Dept of Microbiology

DEPT OF MICROBIOLOGY

Researcher : Bahl J

List of Research Outputs

Guan Y., Dhanasekaran V., Bahl J., Zhu H., Wang J. and Smith G.J., The emergence of pandemic influenza viruses, Protein & Cell. 2010, 1: 9-13.

Smith G.J., Bahl J., Dhanasekaran V., Zhang J., Poon L.L.M., Chen H., Webster R.G., Peiris J.S.M. and Guan Y., Dating the emergence of pandemic influenza viruses, Proceedings of National Academic Science (USA). 2009, 106: 11709-11712.

Researcher : Chan CM

List of Research Outputs

Chan C.M., Lau S.K.P., Woo P.C.Y., Tse H., Zheng B., Chen L., Huang J. and Yuen K.Y., Identification Of Major Histocompatibility Complex Class I C Molecule As An Attachment Factor That Facilitates Coronavirus Hku1 Spike-mediated Infection, Journal of Virology. 2009, 83: 1026-1035.

Kao P.Y.P., Yang D., Lau L.S., Tsui H.W., Hu L., Dai J., Chan M.P., Chan C.M., Wang P., Zheng B., Sun J., Huang J., Madar J., Chen G., Chen H., Guan Y. and Yuen K.Y., Identification of Influenza a Nucleoprotein as an Antiviral Target, Nature Biotechnology. 2010, 28: 600-608.

Researcher : Chan CS

List of Research Outputs

Du L., Zhao G., Chan C.S., Li L., He Y., Zhou Y., Zheng B. and Jiang S., A 219-mer CHO-expressing RBD of SARS-CoV S protein induces potent immune responses and protective immunity. , Viral Immunol. . 2010, 23(2):: 211-219.

Du L., Zhao G., Chan C.S., Sun S., Chen M., Liu Z., Guo H., He Y., Zhou Y., Zheng B. and Jiang S., Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity. , Virology. 2009, 393:: 144-150.

Siu K.L., Chan C.P., Chan C.S., Zheng B. and Jin D., Severe acute respiratory syndrome coronavirus nucleocapsid protein does not modulate transcription of human FGL2 gene., J. Gen. Virol.. 2009, 90: 2107-2113.

Zhao G., Lin Y., Du L., Guan J., Sun S., Sui H., KOU Z., Chan C.S., Guo Y., Jiang S., Zheng B. and Zhou Y., An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses. 9. , Virol J.. 2010, 7(1):: 9.

Zhou J., Huang J., Poon K.M., Chen D., Chan C.S., Ng F., Guan X.Y., Watt R.M., Lu L., Yuen K.Y. and Zheng B., Functional dissection of an IFN-alfa/belta receptor 1 promoter variant that confers higher risk to chronic hepatitis B virus infection. , J Hepat.. 2009, 51(2):: 322-332.

Researcher : Chan JFW

List of Research Outputs

Chan J.F.W., Lau S.K.P., Woo P.C.Y., Fan Y.Y., Ip J.J.K., Chan C.F., Luk J.K.H. and Yuen K.Y., Lactobacillus rhamnosus hepatic abscess associated with Mirizzi syndrome: a case report and review of the literature, Diagnostic Microbiology and Infectious Disease . 2010, 66: 94-97.

Chen H., Cheung C.L., Tai H., Zhao P., Chan J.F.W., Cheng V.C.C., Chan K.H. and Yuen K.Y., Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus, Hong Kong, China, Emerg Infect Dis.. 2009, 15: 1970-2.

Chen H., Wen X., To K.K.W., Wang P., Tse H., Chan J.F.W., Tsoi H.W., Fung K.S.C., Tse C.W.S., Lee R.A., Chan K.H. and Yuen K.Y., Quasispecies of the D225G Substitution in the Hemagglutinin of Pandemic Influenza A(H1N1) 2009 Virus from Patients with Severe Disease in Hong Kong, China, J. Infectious Diseases. 2010, 201: 1517-21.

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Cheng V.C.C., Tai J.W.M., Wong L.M.W., Chan J.F.W., Li W.S., To K.K.W., Hung I.F.N., Chan K.H., Ho P.L. and Yuen K.Y., Prevention of nosocomial transmission of swine-origin pandemic influenza virus A/H1N1 by infection control bundle. , J Hosp Infect 2010. 2010, 74: 271-7.

Li W.S., Chan K.H., To K.K.W., Wong S.S.Y., Ho P.L., Lau S.K.P., Woo P.C.Y., Tsoi H.W., Chan J.F.W., Cheng V.C.C., Zheng B., Chen H. and Yuen K.Y., Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses, Journal of Clinical Virology. 2009, 46: 325-330.

Li W.S., Hung I.F.N., To K.K.W., Chan K.H., Wong S.S.Y., Chan J.F.W., Cheng V.C.C., Tsang O.T., Lai S.T., Lau Y.L. and Yuen K.Y., The natural viral load profile of patients with pandemic swine-origin influenza A H1N1 2009 (pH1N1) and the effect of oseltamivir treatment., Chest. 2010, 137: 759-768.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Lau C.Y., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection, Clin Infect Dis.. 2010, 50: 850-859.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection, Clinical Infectious Disease. 2010, 50: 850-9.

To K.K.W., Wong S.S.Y., Cheng V.C.C., Tang S.F., Li W.S., Chan J.F.W., Seto W.K., Tse H. and Yuen K.Y., Epidemiology and clinical features of Shewanella infection over an eight-year period., Scandinavian journal of infectious diseases. 2010.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 Influenza A virus, Journal of Medical Virology. 2010, 82: 1-7.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Hung I.F.N., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 influenza A virus, J Med Virol. 2010, 82: 1-7.

Woo P.C.Y., Leung S.Y., To K.K.W., Chan J.F.W., Ngan H.Y., Cheng V.C.C., Lau S.K.P. and Yuen K.Y., Internal transcribed spacer region sequence heterogeneity in Rhizopus microsporus: implications on molecular diagnosis in clinical microbiology laboratories, Journal of Clinical Microbiology. 2010, 48: 208-214.

Researcher : Chan KH

List of Research Outputs

Chan K.H., Lai S.T., Poon L.L.M., Guan Y., Yuen K.Y., Peiris J.S.M. and Peiris J.S.M., Analytical sensitivity of rapid influenza antigen detection tests for swine-origin influenza virus (H1N1). , J Clin Virol. . 2009, 45: 205-7.

Chen H., Cheung C.L., Tai H., Zhao P., Chan J.F.W., Cheng V.C.C., Chan K.H. and Yuen K.Y., Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus, Hong Kong, China, Emerg Infect Dis.. 2009, 15: 1970-2.

Chen H., Wen X., To K.K.W., Wang P., Tse H., Chan J.F.W., Tsoi H.W., Fung K.S.C., Tse C.W.S., Lee R.A., Chan K.H. and Yuen K.Y., Quasispecies of the D225G Substitution in the Hemagglutinin of Pandemic Influenza A(H1N1) 2009 Virus from Patients with Severe Disease in Hong Kong, China, J. Infectious Diseases. 2010, 201: 1517-21.

Cheng K.Y., Cowling B.J., Chan K.H., Fang J., Seto W.H., Yung R.W.H., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., Factors affecting QuickVue Influenza A + B rapid test performance in the community setting, Diagnostic Microbiology and Infectious Disease. 2009, 65(1): 35-41.

Cheng V.C.C., Tai J.W.M., Wong L.M.W., Chan J.F.W., Li W.S., To K.K.W., Hung I.F.N., Chan K.H., Ho P.L. and Yuen K.Y., Prevention of nosocomial transmission of swine-origin pandemic influenza virus A/H1N1 by infection control bundle. , J Hosp Infect 2010. 2010, 74: 271-7.

Cheung K.W., Chin W.H., Chan K.H., Schumaker M., Mak W.Y., Leung S.Y.H., Wong A., Peiris J.S.M., Petrauskene O.V. and Poon L.L.M., Evaluation of novel H1N1-specific primer-probe sets using commercial RT-PCR mixtures and a premixed reaction stored in a lyophilized format, Journal of Virological Methods. 2010, 165: 302-4.

Chiu S.S.S., Chan K.H., Chen H., Young B.W., Lim W., Wong W.H.S., Lau Y.L. and Peiris J.S.M., Virologically confirmed population-based burden of hospitalization caused by influenza A and B among children in Hong Kong, Clinical Infectious Diseases. 2009, 49: 1016-1021.

Cowling B.J., Leung G.M., Riley S., Ip D.K.M., Chiu S.S.S., Peiris J.S.M. and Chan K.H., A randomized controlled trial of the effectiveness of FluMist® vaccine in school aged children to reduce infection and transmission of influenza in children and their households (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong. Hong Kong, School of Public Health/HKU, 2009, 21.

Cowling B.J., Chiu S.S.S., Chan K.H., Peiris J.S.M. and Leung G.M., A randomized controlled trial of the effectiveness of vaccinating children to reduce household transmission of influenza (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong. Hong Kong, School of Public Health/HKU, 2009, 20.

Cowling B.J., Chan K.H., Fang J., Cheng K.Y., Fung R.O.P., Lim Wai W.S., Sin J.W.F., Seto W.H., Yung R.W.H., Chu D.W.S., Chiu B., Lee P., Chiu M.C., Lee H.C., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., A randomized trial of face masks and hand hygiene to prevent influenza transmission in households (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong. Hong Kong, School of Public Health/HKU, 2009, 22.

Cowling B.J., Chan K.H., Fang J., Lau L.L.H., So H.C., Fung R.O.P., Ma S.K., Kwong A.S.K., Chan C.W., Tsui W.W.S., Ngai H.Y., Chu D.W.S., Lee P.W.Y., Chiu M.C. and Leung G.M., Comparative epidemiology of pandemic and seasonal influenza A in households, New England Journal of Medicine. 2010, 362: 2175-2184.

Cowling B.J., Chan K.H., Fang J., Cheng K.Y., Fung R.O.P., Lim Wai W.S., Sin J.W.F., Seto W.H., Yung R.W.H., Chu D.W.S., Chiu B.C.F., Lee P.W.Y., Chiu M.C., Lee H.C., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., Facemasks and hand hygiene to prevent influenza transmission in households: a cluster randomized trial, Annals of Internal Medicine. 2009, 151(7): 437-446.

Garcia J., Pepin S., Lagarde N.J.C., Ma S.K., vogel F.R., Chan K.H., Chiu S.S.S. and Peiris J.S.M., Heterosubtype neutralizing responses to influenza A (H5N1) viruses are mediated by antibodies to virus haemagglutinin, PLoS One. 2009, 4(11): e7918.

Lau L.L.H., Fang J., Chan K.H., Ma E., Leung G.M., Peiris J.S.M. and Cowling B.J., Homologous and heterologous immune responses to naturally-acquired influenza virus infection (poster presentation), 14th International Congress on Infectious Diseases, 9-12 March 2010, Miami, USA . Miami, USA, International Congress on Infectious Diseases, 2010, 77.

Lau L.L.H., Cowling B.J., Fang J., Chan K.H., Peiris J.S.M. and Leung G.M., The dynamics between viral shedding and the clinical course of natural influenza infections (Poster presentation), 14th Research Postgraduate Symposium, 2-3 December 2009, Hong Kong. Hong Kong, LKS Faculty of Medicine, HKU, 2009, 96.

Lau L.L.H., Cowling B.J., Fang J., Cheng K.Y., Chan K.H., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., The trajectories of viral shedding, clinical course and tympanic temperature in natural influenza infections (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong. Hong Kong, School of Public Health/HKU, 2009.

Lau L.L.H., Cowling B.J., Fang J., Chan K.H., Lau E.H.Y., Lipsitch M., Cheng K.Y., Houck P.M., Uyeki T.M., Peiris J.S.M. and Leung G.M., Viral shedding and clinical illness in naturally acquired influenza virus infections, Journal of Infectious Diseases. 2010, 201(10): 1509-1516.

Lau S.K.P., Yip C.Y., Lin A.W., Lee R.A., So L.Y., Lau Y.L., Chan K.H., Woo P.C.Y. and Yuen K.Y., Clinical and molecular epidemiology of human rhinovirus C in children and adults in Hong Kong reveals a possible distinct human rhinovirus C subgroup, Journal of Infectious Diseases. 2009, 200(7): 1096-1103.

Lau S.K.P., Chan K.H., Yip C.Y., Ng T.K., Tsang O.T., Woo P.C.Y. and Yuen K.Y., Confirmation of the first Hong Kong case of human infection by novel swine origin influenza A (H1N1) virus diagnosed using ultrarapid, real-time reverse transcriptase PCR, Journal of Clinical Microbiology. 2009, 47: 2344-2346.

Lau S.K.P., Li K.S.M., Huang Y., Shek C.T., Tse H., Wang M., Choi K.Y., Xu H., Lam S.F., Guo R., Chan K.H., Zheng B., Woo P.C.Y. and Yuen K.Y., Ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndrome-related Rhinolophus bat coronavirus in China reveal bats as a reservoir for acute, self-limiting infection that allows recombination events, Journal of Virology . 2010, 84: 2808-2819.

Lau S.K.P., Woo P.C.Y., Wong B.H.L., Wong Y.P., Tsoi H.W., Wang M., Lee P., Xu H., Poon R.W.S., Guo R., Li K.S.M., Chan K.H., Zheng B. and Yuen K.Y., Identification and complete genome analysis of three novel paramyxoviruses, Tuhoko virus 1, 2 and 3, in fruit bats from China, Virology. 2010, 404: 106-116.

Li W.S., Chan K.H., To K.K.W., Wong S.S.Y., Ho P.L., Lau S.K.P., Woo P.C.Y., Tsoi H.W., Chan J.F.W., Cheng V.C.C., Zheng B., Chen H. and Yuen K.Y., Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses, Journal of Clinical Virology. 2009, 46: 325-330.

Li W.S., Hung I.F.N., To K.K.W., Chan K.H., Wong S.S.Y., Chan J.F.W., Cheng V.C.C., Tsang O.T., Lai S.T., Lau Y.L. and Yuen K.Y., The natural viral load profile of patients with pandemic swine-origin influenza A H1N1 2009 (pH1N1) and the effect of oseltamivir treatment., Chest. 2010, 137: 759-768.

Ng S., Cowling B.J., Chan K.H., Chiu S.S.S., Peiris J.S.M. and Leung G.M., A randomized controlled trial of the effectiveness of vaccinating children to reduce household transmission of influenza (Poster presentation), 14th Research Postgraduate Symposium, 2-3 December 2009, Hong Kong. Hong Kong, LKS Faculty of Medicine, HKU, 2009, 86.

Ng S., Cowling B.J., Fang J., Chan K.H., Ip D.K.M., Cheng K.Y., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., Effects of oseltamivir treatment on duration of clinical illness and viral shedding and household transmission of influenza virus, Clinical Infectious Diseases. 2010, 50(5): 707-714.

Poon L.L.M., Chan K.H., Smith G.J., Leung C.S.W., Guan Y., Yuen K.Y. and Peiris J.S.M., Molecular detection of a novel human influenza (H1N1) of pandemic potential by conventional and real-time quantitative RT-PCR assays., Clin Chem.. 2009, 55: 1555-8.

Poon L.L.M., Mak W.Y., Li O.T.W., Chan K.H., Cheung C.L., Ma S.K., Yen H., Dhanasekaran V., Guan Y. and Peiris J.S.M., Rapid Detection of Reassortment of Pandemic H1N1/2009 Influenza Virus, Clinical Chemistry. 2010, 56: 1340-4.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Lau C.Y., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection, Clin Infect Dis.. 2010, 50: 850-859.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection, Clinical Infectious Disease. 2010, 50: 850-9.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 Influenza A virus, Journal of Medical Virology. 2010, 82: 1-7.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Hung I.F.N., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 influenza A virus, J Med Virol. 2010, 82: 1-7.

Wong C.M., Yang L., Chan K.P., Ma S., He J.F., Chen P., Chan K.H. and Peiris J.S.M., Disease burden of influenza in three tropic and subtropic cities in Asia (powerpoint presentation), MISMS Oceania Regional Meeting and Workshop, 15-19 March 2010, Melbourne. Melbourne, National Institutes of Health, 2010.

Wong C.M., Yang L., Chan K.P., Chan K.H., Hedley A.J. and Peiris J.S.M., Influenza-associated hospitalisation, Hong Kong Medical Journal. 2009, 15(6) Suppl: S35-S37.

Wong C.M., Chiu S.S.S., Yang L., Wong T.W., Ma S., He J.F., Chen P., Chan K.P., Chan K.H., Wong W.H.S. and Peiris J.S.M., The burden of seasonal influenza in Hong Kong: A model-based approach with validation and comparison with other tropical/subtropical cities (poster presentation), MISMS Oceania Regional Meeting and Workshop, 15-19 March 2010, Melbourne. Melbourne, National Institutes of Health, 2010.

Woo P.C.Y., Lau S.K.P., Lam S.F., Lai K.Y., Huang Y., Lee P., Luk G.S.M., Dyrting K.C., Chan K.H. and Yuen K.Y., Comparative Analysis Of Complete Genome Sequences Of Three Avian Coronaviruses Reveals A Novel Group 3c Coronavirus, Journal of Virology. 2009, 83: 908-917.

Woo P.C.Y., Tung T.K., Chan K.H., Lau C.Y., Lau S.K.P. and Yuen K.Y., Cytokine profiles induced by the novel swine-origin influenza A/H1N1 virus: implications for treatment strategies, Journal of Infectious Diseases. 2010, 201: 346-353.

Yang L., Wong C.M., Chan K.P., Chau Y.K., Ou C., Chan K.H. and Peiris J.S.M., Seasonal effects of influenza on mortality in a subtropical city, BMC Infectious Diseases. 2009, 9: 133.

Yip C.Y., Lau S.K.P., Zhou B., Zhang M.X., Tsoi H.W., Chan K.H., Chen X.C., Woo P.C.Y. and Yuen K.Y., Emergence of enterovirus 71 "double-recombinant" strains belonging to a novel genotype D originating from southern China: first evidence for combination of intratypic and intertypic recombination events in EV71., Archives of Virology. 2010.

Researcher : Chan MCW

Project Title:	Replication and pathogenesis of avian influenza A (H5N1) viruses in polarized human bronchial and alveolar epithelium
Investigator(s):	Chan MCW, Tsao GSW, Peiris JSM, Chan WY
Department:	Microbiology
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	03/2007

Abstract:

To establish a well differentiated and polarized primary human respiratory epithelial cell model in vitro to study and compare the replication kinetics of avian influenza H5N1 and H1N1 viruses. This model will provide insights into the pathogenesis of H5N1 disease in the lung. The role of innate immune response mediators and molecules such as mucin, collectins and glycoprotein-340 on viral replication will be investigated. The Contribution of different avian or human influenza viral genes to the viral replication and cytokine induction will be defined using recombinant influenza viruses generated by reverse genetics.

Project Title:	Tissue tropism and innate immune responses of respiratory viruses in primary differentiated human respiratory epithelial cells in vitro and in ex-vivo cultures of lung and nasopharynx
Investigator(s):	Chan MCW, Nicholls JM, Poon LLM, Tsao GSW
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	12/2008

Abstract:

(1) Compare the tropism of different human respiratory viruses to human upper and lower respiratory epithelium using polarized and differentiated in vitro models of respiratory epithelial cells and ex-vivo cultures of the upper (nasopharyngeal, tonsillar) and lower (lung) respiratory tract; (2) Compare the innate immune response, including but not limited to type 1 interferon responses, induced by human respiratory viruses in polarized and differentiated primary human respiratory epithelial cells.

Project Title:	Effect of vitamin B2 in the treatment of human influenza H5N1 virus infection: studies in vitro and in vivo
Investigator(s):	Chan MCW, Peiris JSM, Chan WY
Department:	Microbiology
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	02/2009

Abstract:

To demonstrate the beneficial effect of vitamin B2 as potentially effective treatment of human H5N1 disease by studying the signaling pathways involved in modulating the differential pro-inflammatory cytokines induction upon avian influenza H5N1 virus infection.

Project Title:	Role of Toll-like receptors and MyD88 in the innate immune response elicited by highly pathogenic influenza A (H5N1) virus infection in vivo
Investigator(s):	Chan MCW
Department:	Microbiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2009

Abstract:

Background: The current outbreak of highly pathogenic avian influenza H5N1 is unprecedented in geographical extent and poses a major pandemic threat. The pathogenesis of the severe human disease and case fatality associated with H5N1 infection remains unclear. We previously demonstrated that H5N1 viruses were more potent inducers of proinflammatory cytokines from human respiratory epithelial cells and macrophages, and that patients with H5N1 disease have higher serum levels of IP-10, IL-8 and other chemokines than those infected with human influenza viruses. These findings have led to the hypothesis that cytokine dysregulation may play a role in the pathogenesis of H5N1 disease. The release of high levels of proinflammatory cytokines would aggravate inflammation and further stimulate their release through a positive feedback mechanism leading to a “cytokine storm”. The molecular basis of this cytokine hyper-induction is unknown. We aim to investigate the role of toll-like receptor (TLR) pathway in differential cytokine induction and pathogenesis in a mouse model. As pilot studies, in vitro mouse macrophages and epithelail cells culture models will be used to identify the signaling pathway activated by infection. We propose to investigate the cellular receptors and their cytoplasmic adaptor, which are important in sensing of invading microbes and initiating host defense using specifc knock-out mouse models. These in vivo models are useful tools to identify possible pathways which may be responsible for the cytokines hyper-induction. Objective: To use gene knock-out mice to investigate the role of TLRs and MyD88 in the induction of a) pro-inflammatory cytokines, b) chemokines and c) type-I interferon in knock-out mice infected with influenza H5N1 viruses in vivo. Design and study plan: To investigate gene expression of cytokines, TLRs and MyD88 associated with influenza H5N1 virus infection in mouse in vivo studies. This is to demonstrate the possible roles of influenza H5N1 virus as the hyper-inductor of pro-inflammatory cytokines. In vivo studies (viral titer determination, cytokines assay and histopathology study) comparing the TLRs and MyD88 gene knock-out mice will be done to investigate the role of TLRs and MyD88 as a potential signaling pathway in the pathogenesis of human H5N1 disease. Main outcome: With the availability of specific gene knock-out strains, mouse is an useful in vivo tools to study the pathogenesis of highly pathogenic avian influenza H5N1 viruses. Understanding the host interaction with virus can provide important insight into the mechanism of pathogenesis and to identify the possible signaling pathways in the innate immune response with respect to H5N1 virus. The information can lead to a more rational postulation on the severity of human H5N1 disease

Project Title:	28th Annual Meeting of American Society for Virology Infection of influenza A (H5N1) virus in human eye epithelium, an in vitro and ex vivo study
Investigator(s):	Chan MCW
Department:	Microbiology
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	07/2009
Completion Date:	07/2009

Abstract:

N/A

Project Title:	Influenza A (H5N1) virus infection in human primary type I and type II alveolar epithelial cells: Cell tropism, inflammatory responses and apoptosis
Investigator(s):	Chan MCW, Peiris JSM
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2010

Abstract:

1) To establish a physiologically relevant in vitro cell model of alveolar epithelial type II cells (ATII), alveolar epithelial type I cells (ATI) and alveolar macrophages (AMs); 2) To determine the cell tropism of highly pathogenic influenza H5N1 viruses and other low pathogenic human and avian influenza virus (H1N1, H3N1, H9N2, H5N8, etc) in human ATII, ATI cells and AMs using in vitro cell model; 3) To compare the innate immune responses induced by H5N1 virus and low pathogenic human (H1N1) and avian influenza (H9N2, H5N8) viruses in human ATII, ATI cells and AMs; 4) To compare the caspase 1 induced maturation and secretion of IL1-β (i.e. activation of inflammasome) in ATII, ATI cells and AMs infected with HPAI H5N1 virus and LPAI human (H1N1) or avian (H9N2, H5N8) viruses; 5) To compare the induction of apoptosis in ATII, ATI cells and AMs infected with HPAI H5N1 and LPAI human (H1N1) or avian (H9N2, H5N8) viruses; 6) To investigate the role of TNFsrp, IL-1Ra, and IL-18 binding protein in the inhibition of influenza virus induced release of cytokines and chemokines; 7) To determine the effect of infection by H5N1 virus and low pathogenic human (H1N1) and avian influenza (H9N2, H5N8) viruses on regeneration of ATI cells from the ATII cell precursors.

List of Research Outputs

Chan M.C.W., Chan W.Y., Yu C.L., Ho C.C., Chui W.H., Lo C.K., Yuen K.M., Guan Y., Nicholls J.M. and Peiris J.S.M., Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells, Respiratory Research. 2009, 10: 102.

Chan M.C.W., Chan W.Y., Yu C.L., Ho C.C., Yuen K.M., Fong J.H.M., Tang L.L.S., Lai W.W.K., Lo A.C.Y., Chui W.H., Sihoe A.D.L., Kwong D.L.W., Tsao G.S.W., Poon L.L.M., Guan Y., Nicholls J.M. and Peiris J.S.M., Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract, American Journal of Pathology. 2010, 176(4): 1828-40.

Chan W.Y., Chan M.C.W., Wong C.N., Karamanska R., Dell A., Haslam S.M., Sihoe A.D., Chui W.H., Triana-Baltzer G., Li Q., Peiris J.S.M., Fang F. and Nicholls J.M., DAS181 Inhibits H5N1 Influenza virus Infection of Human Lung Tissues., Antimicrobial Agents and Chemotherapy. 2009, 53(9): 3935-3941.

Chan W.Y., Yuen K.M., Yu C.L., Ho C.C., Nicholls J.M., Peiris J.S.M. and Chan M.C.W., Differential Viral Replication Kinetics And Host Innate Immune Responses By Influenza A (H5N1) Virus In Human Bronchial Epithelial Cells At Different Differentiation Stages, The 28th Annual meeting of American Society for Virology. 2009.

Chan W.Y., Yu C.L., Yuen K.M., Fong J.H.M., Lo A.C.Y., Lai W.W.K., Wong D.S.H., Nicholls J.M., Peiris J.S.M. and Chan M.C.W., Infection of influenza A (H5N1) virus in human eye epithelium, an in vitro and ex vivo study , The 28th Annual Meeting of the American Society of Virology. 2009.

Chan W.Y., Yuen K.M., Yu C.L., Ho C.C., Nicholls J.M., Peiris J.S.M. and Chan M.C.W., Influenza H5n1 And H1n1 Virus Replication And Innate Immune Responses In Bronchial Epithelial Cells Are Influenced By The State Of Differentiation, PLoS One. 2010, 5 (1): e8713.

Chan W.Y., Chan M.C.W., Nicholls J.M. and Peiris J.S.M., Tropism and host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract , XII International Symposium on Respiratory Viral Infections. 2010.

Mok K.P., Wong C.H.K., Cheung C.Y., Chan M.C.W., Lee M.Y., Nicholls J.M., Guan Y. and Peiris J.S.M., Viral Genetic Determinants of H5N1 Influenza Viruses That Contribute to Cytokine Dysregulation, Journal of Infectious Diseases. 2009, 200(7): 1104-12.

Triana-Baltzer G.B., Babizki M., Chan M.C.W., Wong A.C.N., Aschenbrenner L.M., Campbell E.R., Li Q.X., Chan W.Y., Peiris J.S.M., Nicholls J.M. and Fang F., DAS181, a sialidase fusion protein, protects human airway epithelium against influenza virus infection: an in vitro pharmacodynamic analysis., J Antimicrob Chemother. 2010, 65: 275-84.

Triana-Baltzer G.B., Gubareva L.V., Nicholls J.M., Pearce M.B., Mishin V.P., Belser J.A., Chen L.M., Chan W.Y., Chan M.C.W., Hedlund M., Larson J.L., Moss R.B., Katz J.M., Tumpey T.M. and Fang F., Novel pandemic influenza A(H1N1) viruses are potently inhibited by DAS181, a sialidase fusion protein, PLoS One. 2009, 4: e7788.

Triana-Baltzer G.B., Gubareva L.V., Nicholls J.M., Pearce M.B., Mishin V.P., Belser J.A., Chen L.M., Chan W.Y., Chan M.C.W., Klimov A.A., Hedlund M., Wurtman D., Moss R.B., Katz J.M., Tumpey T.M., Belshe R.B. and Fang F., Pandemic H1N1 2009 and Drug Resistant Influenza Viruses are Potently Inhibited by DAS181, a Sialidase Fusion Protein, Interscience Conference on Antimicrobial Agents and Chemotherapy. 2009.

Researcher : Chan MP

List of Research Outputs

Kao P.Y.P., Yang D., Lau L.S., Tsui H.W., Hu L., Dai J., Chan M.P., Chan C.M., Wang P., Zheng B., Sun J., Huang J., Madar J., Chen G., Chen H., Guan Y. and Yuen K.Y., Identification of Influenza a Nucleoprotein as an Antiviral Target, Nature Biotechnology. 2010, 28: 600-608.

Researcher : Chen D

List of Research Outputs

Chen D. and Zheng B., Association of candidate susceptible loci with chronic hepatitis B virus infection in Chinese population. ., European Congress of Clinical Microbiology and Infectious Diseases. Vienna, Austria. 2010.

Chen D., Zeng Y., Zhou J., Yang L., Jiang S., Huang J., Lu L. and Zheng B., Association of candidate susceptible loci with chronic infection with hepatitis B virus in a Chinese population. , J Med Virol.. 2010, 82(3):: 371-378.

Zhou J., Huang J., Poon K.M., Chen D., Chan C.S., Ng F., Guan X.Y., Watt R.M., Lu L., Yuen K.Y. and Zheng B., Functional dissection of an IFN-alfa/belta receptor 1 promoter variant that confers higher risk to chronic hepatitis B virus infection. , J Hepat.. 2009, 51(2):: 322-332.

Researcher : Chen H

Project Title:	Modification of cells for isolation and characterization of SARS CoV from animal sources
Investigator(s):	Chen H
Department:	Microbiology
Source(s) of Funding:	Seed Funding for New Staff
Start Date:	07/2004

Abstract:

To provide: (1) a panel of cell lines (pools) for the isolation of SARS CoV from animal sources; (2) information on molecular mechanism of interspecies transmission of SARS CoV; (3) clues for the further molecular virology studies on this virus.

Project Title:	Biological function/relevance for the 29 nucleotides insertion in the genome of animal SARS like CoV
Investigator(s):	Chen H, Guan Y
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

This study will serve as a pilot investigating the potential effect of insertion/deletion on expression of viral proteins down stream of this region and provide clues for further investigation into the molecular mechanism for SARS coronavirus interspecies transmission.

Project Title:	Antiviral drug resistance in H5N1 virus
Investigator(s):	Chen H, Guan Y
Department:	Microbiology
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	01/2007

Abstract:

To investigate the geographical distribution of resistance mutations to amantadine and rimantadine in H5N1 isolates from different regions, and to explore if low frequency naturally occuring mutations associated with resistance to oseltamivir are present in H5N1 isolates and if they may contribute to the emergence of oseltamivir resistant strains following exposure to this drug.

Project Title:	H5N1 virus heterogeneity and mechanisms for adaptation to new hosts
Investigator(s):	Chen H, Guan Y
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2007

Abstract:

To investigate the distribution of L26I and S31N M2 mutants and H274Y NA mutants among H5N1 isolates from different geographical locations isolated at different points in time; to compare the growth and transmissibility phenotypes of mutants with wild type virus in different hosts, particularly chickens and mice; to study the growth advantage/disadvantage of M2 and NA H5N1 virus mutants in their new hosts, which will provide information on whether such mutants have the potential to gradually increase their presence and/or outgrow wild type virus to become the dominant population; to study the biological fitness of viruses carrying M2 or NA mutations in mammals and explore the pandemic potential of H5N1 virus.

Project Title:	Mapping antigenic sites on haemagglutinin antigen (HA) of H5N1 virus with a panel of H5 specific monoclonal antibodies.
Investigator(s):	Chen H, Guan Y
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2008
Completion Date:	12/2009

Abstract:

To raise, characterize and continuously update monoclonal antibodies against H5N1 virus of different genetic background with antigens representing different genetic lineages of virus strains, which will provide most needed reagents for the diagnosis and viral antigenicity studies; to characterize antigenic profile of H5N1 virus from different genetic lineages with these monoclonal antibodies; to map antigenic sites on HA of H5N1 virus with escape mutant assay and neutralization test. Current recommended H5N1 vaccine candidates elicit poor immune responses in hosts, in particular mammals. This study will investigate the antigenic elements in H5N1 virus and provide information for vaccine selection; to use reverse genetic technology and the data of antigenicity obtained above to modify H5N1 virus HA gene to prepare vaccine candidate with a broad cross reactivity.

List of Research Outputs

Bao L., Xu L., Zhang L., Deng W., Zhu H., Gao H., Sun H., Ma C., Lv Q., Li F., Chen H., Zhang L. and Qin C., Challenge and polymorphism analysis of the novel A (H1N1) influenza virus to normal animals, Virus Research. 2010, 151: 60-65.

Chen H., Cheung C.L., Tai H., Zhao P., Chan J.F.W., Cheng V.C.C., Chan K.H. and Yuen K.Y., Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus, Hong Kong, China, Emerg Infect Dis.. 2009, 15: 1970-2.

Chen H., Wen X., To K.K.W., Wang P., Tse H., Chan J.F.W., Tsoi H.W., Fung K.S.C., Tse C.W.S., Lee R.A., Chan K.H. and Yuen K.Y., Quasispecies of the D225G Substitution in the Hemagglutinin of Pandemic Influenza A(H1N1) 2009 Virus from Patients with Severe Disease in Hong Kong, China, J. Infectious Diseases. 2010, 201: 1517-21.

Chen H., Wang Y., Liu W., Zhang J., Dong B., Fan X., Jong M.D., Farrar J., Riley S., Smith G.J. and Guan Y., Serology survey of pandemic (H1N1) 2009 virus, Guangxi Province, China, Emerging Infectious Diseases. 2009, 15: 1849-50.

Chen H., Special recognition award for extraordinatory work in H1N1 influenza reserch. , National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases . 2010.

Chen Y., Xu F., Gui X., Yang K., Wu X., Zheng Q., Ge S., Yuan Q., Yeo A... .E...T..., Zhang J., Guan Y., Chen H. and Xia N., A rapid test for the detection of influenza A virus including pandemic influenza A/H1N1 2009, J Virol Methods. 2010, 167: 100-2.

Chen Y., Luo W., Wu W.L., Fang Z., Xia L., Gui X., Chen Y., Chen H., Shih J.W.K. and Xia N., Humanized Antibodies with Broad-Spectrum Neutralization to Avian Influenza Virus H5N1, Antiviral Research. 2010, 87: 81-4.

Fang Y., Rowe T., Leon A.J., Banner D., Danesh A., Xu L., Ran L., Bosinger S.E., Guan Y., Chen H., Cameron C.C., Cameron M.J. and Kelvin D.J., Characterization of in vivo Adjuvant Activity in Influenza-Vaccinated Ferrets, J Virol. 2010, 84: 8369-88.

Kao P.Y.P., Yang D., Lau L.S., Tsui H.W., Hu L., Dai J., Chan M.P., Chan C.M., Wang P., Zheng B., Sun J., Huang J., Madar J., Chen G., Chen H., Guan Y. and Yuen K.Y., Identification of Influenza a Nucleoprotein as an Antiviral Target, Nature Biotechnology. 2010, 28: 600-608.

Li W.S., Chan K.H., To K.K.W., Wong S.S.Y., Ho P.L., Lau S.K.P., Woo P.C.Y., Tsoi H.W., Chan J.F.W., Cheng V.C.C., Zheng B., Chen H. and Yuen K.Y., Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses, Journal of Clinical Virology. 2009, 46: 325-330.

Liu N., Song W., Wang P., Lee K.C., Cai Z. and Chen H., Identification of unusual truncated forms of nucleocapsid protein in MDCK cells infected by Avian influenza virus (H9N2), Proteomics. 2010, 10: 1875-1879.

Liu N., Wang G., Lee K.M., Guan Y., Chen H. and Cai Z., Mutations in influenza virus replication and transcription: detection of amino acid substitutions in hemagglutinin of an avian influenza virus (H1N1), FASEB J.. 2009, 23: 3377-82.

Ma B.Y., Lui V.W.Y., Poon F.F., Wong S.C.C., To K.F., Wong E., Chen H., Lo K.W., Tao Q. and Chan A.T.C., Preclinical activity of gefitinib in non-keratinizing nasopharyngeal carcinoma cell lines and biomarkers of response, Invest New Drugs. 2010, 28: 326-333.

Smith G.J., Bahl J., Dhanasekaran V., Zhang J., Poon L.L.M., Chen H., Webster R.G., Peiris J.S.M. and Guan Y., Dating the emergence of pandemic influenza viruses, Proceedings of National Academic Science (USA). 2009, 106: 11709-11712.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Lau C.Y., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection, Clin Infect Dis.. 2010, 50: 850-859.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection, Clinical Infectious Disease. 2010, 50: 850-9.

Tsang C.M., Zhang G., Seto E., Takada K., Deng W., Yip Y.L., Man C.W.Y., Hau P.M., Chen H., Cao Y., Lo K.W., Middeldorp J.M., Cheung A. and Tsao G.S.W., Epstein-Barr virus infection in immortalized nasopharyngeal epithelial cells: Regulation of infection and phenotypic characterization. , International Journal of Cancer. 2010, 127: 1570-1583.

Tsao G.S.W., Tsang C.M., Zhang G., Deng W., Hau P.M., Man C.W.Y., Kenzo T., Chen H., Yip Y.L., Lo K.W., Cao Y. and Cheung A., Epstein-Barr virus infection confer stress-resistant property in immortalized nasopharyngeal epithelial cells., Proceedings of American Association of Cancer Research. 2010.

Yip Y.L., Tsang C.M., Jin Y., Deng W., Man C.W.Y., Cheung P.P.Y., Chen H., Cheung A. and Tsao G.S.W., The Epstein-Barr virus-encoded LMP1 extended the life span and immortalized nasopharyngeal epithelial cells., Hong Kong International Cancer Congress . 2009.

Zhang J., Zhang Z., Fan X., Liu Y., Wang J., Zheng Z., Chen R., Wang P., Song W., Chen H. and Guan Y., 2009 pandemic H1N1 influenza virus replicates in human lung tissues, J Infect Dis. 2010, 201: 1522-6.

Zheng Z., Luo W., Song H., Chen Y., Xiong J., Chen Y., Gu Y., Chen H., Shih J.W.K., Zhang J. and Xia N., Antibody reactivity of conformational peptide mimics of a conserved H5N1 neutralization site in different fusion proteins, Arch Virol.. 2010, 155: 19-26.

Zhu H., Wang J., Wang P., Song W., Zheng Z., Chen R., Guo K., Zhang T., Peiris J.S.M., Chen H. and Guan Y., Substitution of lysine at 627 position in PB2 protein does not change virulence of the 2009 pandemic H1N1 virus in mice, Virology. 2010, 401: 1-5.

Researcher : Chen JHK

Project Title:	Influence of amino acid insertion at codon 35 in the protease region of the HIV-1 pol gene on drug resistance
Investigator(s):	Chen JHK, Yam WC
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	10/2008
Completion Date:	09/2009

Abstract:

Protease insert HIV strains were reported in less than 0.1% patients worldwide and little is known about their impact on viral fitness and drug resistance towards protease inhibitors. Amino acid insertion at codon 35 of protease occurred in 0.04% among 25,330 patients (Kim et al, 2001; Paolucci et al, 2006). In collaboration with Integrated Treatment Centre of the Department of Health, a 3-year study supported by AIDS Trust Fund (project number MS099) revealed this insertion was more prevalent and occurred at 1.3% among 924 HIV+ patients in Hong Kong. Detailed investigation on the influence of this insertion to Protease inhibitor resistance will facilitate better clinical management of HIV infections in Hong Kong The specific objectives of this project emphasis on the association of amino acid insertion at the protease codon 35 position of the HIV-1 pol gene with drug resistance against different FDA-approved Protease inhibitors.

Project Title:	Molecular epidemiology study of HIV-1 among the men who have sex with men (MSM) population in Hong Kong
Investigator(s):	Chen JHK, Yam WC
Department:	Microbiology
Source(s) of Funding:	Council for the AIDS Trust Fund - General Award
Start Date:	04/2009

Abstract:

To elaborate the epidemiology of the local MSM population who is responsible for the local spread of HIV-1 in Hong Kong by: (1) Sequencing of the HIV-1 viral genes (pol and env) of 60 recently HIV-1 infected MSM in Hong Kong and performing phylogenetic analyses to identify the local MSM population who have close epidemiological relationships. (2) Development of a low costing in-house molecular method for monitoring of HIV-1 transmission among MSM in Hong Kong. (3) Monitoring the presence of primary resistance HIV-1 isolates in the local MSM population.

List of Research Outputs

Chen J.H.K., Wong K.H., Li P., Chan K.C., Lee M.P., Lam H.Y., Cheng V.C., Yuen K.Y. and Yam W.C., Molecular epidemiological study of HIV-1 CRF01_AE transmission in Hong Kong. , Journal of acquired immunodeficiency syndromes. USA, 2009, 51(5): 530-535.

Lee S.S., Tam D.K., Tan Y., Mak W.L., Wong K.H., Chen J.H.K. and Yam W.C., An exploratory study on the social and genotypic clustering of HIV infection in men having sex with men. , AIDS. USA, 2009, 23(13): 1755-1764.

Researcher : Chen M

List of Research Outputs

Du L., Zhao G., Chan C.S., Sun S., Chen M., Liu Z., Guo H., He Y., Zhou Y., Zheng B. and Jiang S., Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity. , Virology. 2009, 393:: 144-150.

Zhang G., Chen M. and Zheng B., Development of recombinant Adeno-associated virus vector delivering short-hairpin RNAs to inhibit the replication of influenza. , European Congress of Clinical Microbiology and Infectious Diseases. Vienna, Austria.. 2010.

Researcher : Chen R

List of Research Outputs

Zhang J., Zhang Z., Fan X., Liu Y., Wang J., Zheng Z., Chen R., Wang P., Song W., Chen H. and Guan Y., 2009 pandemic H1N1 influenza virus replicates in human lung tissues, J Infect Dis. 2010, 201: 1522-6.

Researcher : Chen Z

Project Title:	A novel model for the study of lung pathogenesis of SARS
Investigator(s):	Chen Z
Department:	Medical Faculty
Source(s) of Funding:	National Institutes of Health, US Department of Health and Human Services - General Award
Start Date:	08/2007

Abstract:

To characterize the lung pathogenesis of SARS-CoV in Chinese rhesus monkeys.

Project Title:	Understanding the Ongoing HIV Epidemic in Yunnan China
Investigator(s):	Chen Z
Department:	Medical Faculty
Source(s) of Funding:	China AIDS Initiative - General Award
Start Date:	05/2008

Abstract:

To study the changing patterns of HIV-1 epidemic in Yunnan. We hypothesize that the identification of the dominant recombinant type of HIV-1 in Yunnan will play a fundamental role in the design of a relevant vaccine for the study region. While the virus spreads rapidly throughout the Yunnan province, the viral subtype of the dominant epidemic strains have also evolved in an unexpected dynamic way. In 1989, the subtype B virus was found to be the leading causative agent for the first HIV-1 epidemic in Yunnan. Two years later, subtype B′ strains were reported to have become the major epidemic strain. Thereafter, a rising epidemic of Indian subtype C viruses was reported. From our recent study, it is clear that none of these early strains of HIV-1 plays a major role in the epidemic today. Although the driving force for the viral selection remains unclear, the coexistence of multiple genotypes among the same IDU population has provided an ideal setting for the emergence of recombinant HIV-1 strains. We therefore propose to study the evolving HIV-1 epidemic in Yunnan.

Project Title:	Preventing HIV-1 infection using a novel vaccine immunogen
Investigator(s):	Chen Z
Department:	Medical Faculty
Source(s) of Funding:	Global Health Grants
Start Date:	10/2008

Abstract:

Despite over 25 years of efforts, the development of an effective AIDS vaccine to prevent HIV-1 infection remains the biggest challenge in HIV/AIDS research. Considering that conventional vaccine strategies are not successful for HIV-1 prevention, we propose to change the situation by exploring new approaches that follow the fundamental rules of primate evolution and immunology. Specifically, we hypothesize that a variant of simian CCR5 (sCCR5) would be an AIDS vaccine candidate for humans if it induces protective immune response in SHIV/macaque models. This hypothesis is based on findings that (1) CCR5-tropic HIV-1 is transmitted dominantly through sexual contacts; (2) individuals with homozygote delta32-CCR5 are resistant to HIV-1 infection; (3) some long-term non-progressors harboring anti-CCR5 antibodies have much delayed disease progression; and (4) HIV-infected women, who developed anti-CCR5 antibodies, display a lower rate of vertical transmission. Furthermore, we previously demonstrated that (1) both HIV and SIV use CCR5 of several simian species as a major co-receptor for entering target cells (Chen et al. JV. 97, 71:2705), and (2) CCR5 is dispensable in non-human primate species (e.g. red-capped mangabeys; Chen et al. JEM. 98, 188:2057) similar to human cases with homozygote delta32-CCR5. Importantly, our recent preliminary studies indicate that anti-rhesus CCR5 antibody blocks HIV-1 infection in cells expressing human CD4 and CCR5. Since anti-human CCR5 monoclonal antibody 2D7, that has potent neutralizing activity against HIV-1, does not recognize rhesus CCR5, our data indicate that there must be additional neutralizing determinants offering cross-protective response. The objective of the proposal is, therefore, to determine the efficacy of mutants of sCCR5 as AIDS vaccine candidates. The rationale is that if a sCCR5 mutant is protective in macaques against SHIV infection, it would be potentially effective in preventing HIV-1 infection in humans. The proposal includes two specific aims: (1) to design and construct mutants of sCCR5 which are capable of inducing neutralizing antibodies against HIV-1 infection in animals including rhesus macaques; and (2) to determine the efficacy of an optimized sCCR5 mutant using SHIV/Macaque models.

Project Title:	Mucosal Vaccine against HIV-1 Infection
Investigator(s):	Chen Z
Department:	Medical Faculty
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2008

Abstract:

(1) To study a MVTT-HIVenv/gag-pol vaccine which preferentially targets mucosa; (2) To study a MVTT-HIVenv/gag-pol vaccine which evades pre-existing anti-vaccinia immunity.

Project Title:	Role of the PD-1/PD-L pathway in HIV DNA vaccine design
Investigator(s):	Chen Z
Department:	Medical Faculty
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2009

Abstract:

The programmed death 1 (PD-1, also called PDCD1 or CD279) is a member of the CD28 family and is expressed on activated T cells, natural killer T cells (NKT), B cells, and macrophages. PD-1 is a 50-55 kDa type I transmembrane receptor consisting of a single immunoglobulin (Ig) variable-like domain and a cytoplasmic domain composed of two tyrosine-based signaling motifs. PD-1 interacts with its ligands PD-L1 (CD274 or B7-H1) and PD-L2 (CD273 or B7-DC), which are members of B7 family. PD-L1 is expressed on hematopoietic and non-hematopoietic cells, in immunoprivileged sites (eye, placenta), and is highly expressed in inflammatory environments. Upon general activation of the immune response, professional antigen presentation cells (APCs) and T cells further augment PD-L1 expression. By contrast, PD-L2 is expressed only on activated macrophages and dendritic cells (DCs). Some studies have demonstrated the inhibitory function of the PD-1/PD-L pathway (including PD-1/PD-L1 and PD-1/PD-L2). For example, PD-1 is persistently up-regulated on HBV and HCV-specific CD8+ T cells during chronic infection in humans. These virus-specific CD8+ T cells displayed poor proliferation, cytokines production and cytotoxicity. Critically, blocking the PD-1/PD-L1 interaction can reverse the exhausted cytokine production and proliferation of viral specific-CD8+ T cells. Therefore, PD-1 is a pivotal negative immune regulator associated with the establishment of viral chronic infection. Importantly, when antibodies were used to block the PD-1/PD-L pathway in vivo during chronic LCMV infection, virus-specific CD8 T cell responses were potently enhanced. Not only was the number of LCMV-specific CD8 T cells increased dramatically, but their function was also improved. After in vivo PD-1/PD-L blockade, virus-specific CD8 T cells produced more IFN- and TNF- on a per cell basis. The reversal of virus-specific CD8 T cell exhaustion has resulted in a considerable reduction in viral load. These findings provide scientific evidence for investigations into the PD-1/PD-L pathway for new vaccine design. An effective vaccine works by inducing memory immune responses that are capable of expanding to control an incoming infection to limit disease and transmission. B cells and T cells are the two major types of memory cells which need to be induced by the vaccine. B cells produce antibody that can block viral entry and infections. CD8 T cells, also called cytolytic T cells, recognize and kill virus-infected cells. CD4 T cells, often called helper T cells, produce growth and differentiation factors for CD8 T and B cells. To date, classical approaches to vaccine development have not yielded an effective HIV-1 vaccine. New approaches, however, using DNA vaccines, recombinant viral vectors, and combinations of different vectors in heterologous prime/boost regimens are encouraging and yielding vaccines capable of controlling pathogenic AIDS virus challenges in non-human primate models. Therefore, four major approaches have currently been used for the development of a HIV-1 vaccine: (1) delivering antigen in DNA vaccines; (2) delivering antigen in recombinant viral vectors; (3) delivering adjuvanted antigen; and (4) combining two or more modalities for antigen delivery in heterologous prime/boost regimens. DNA vaccines have the advantage of expressing only the vaccine insert. This advantage results in a highly focused immune response. They also have no issues of pre-existing immunity. However, the efficiency of DNA vaccines has been limited in humans probably due to several factors. One factor is the relatively poor ability of DNA to get into cells. This problem is being approached by a number of techniques, including lipofection, gene guns, attaching DNA to particles, and using in vivo electroporation techniques. Another factor is related to poor protein expression and therefore HIV-1 genes optimized for the codons preferred by human cells are used to enhance vaccine insert expression. An additional factor is related to antigen presentation and therefore much work has focused on adjuvants, many of which have been co-expressed by DNA. As a novel strategy, improving vaccine potency by promoting in vivo antigen targeting to dendritic cells has recently been described. By targeting the encoded protein to dendritic cells, a DNA vaccine encoding an HIV-1 gag p41–scFv DEC205 fusion protein induced 10-fold higher antibody levels and increased numbers of IFN- –producing CD4+ and CD8+ T cells. These studies open a new area of HIV-1 vaccine research and have provided scientific evidence in support of this proposed study. Till now, however, it remains unknown whether or not the efficacy of DNA vaccination would be much improved if the vaccine design engages DC targeting while blocks the PD-1/PD-L interaction. DNA vaccination remains at the forefront of efforts aimed at developing vaccine against viral infections including HIV-1. In this study, we hypothesize that targeting vaccine antigens at DCs and blocking the PD-1/PD-L pathway would increase the immunity and protection that result from DNA vaccines. To determine this hypothesis, we will generate a DNA vaccine encoding a fusion protein comprised of the vaccine antigen (e.g. HIV-1 Gag) and a soluble domain of PD-1 (sPD-1) specific for the DC-expressing ligand PD-L. We will focus on two specific objectives. Objective 1: To study the involvement of dendritic cells in sPD-1 based vaccine design in vitro. Objective 2: To study sPD-1-based HIV-1 DNA vaccine in vivo.

Project Title:	AIDS Vaccine 2009 Effective Control of a pathogenic SIVmac239 challenge by a novel heterologous mucosal prime intramuscular boost vaccination strategy
Investigator(s):	Chen Z
Department:	Medical Faculty
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2009
Completion Date:	10/2009

Abstract:

N/A

Project Title:	Role of the PD-1/PD-L pathway in HIV-1 vaccine design
Investigator(s):	Chen Z
Department:	Medical Faculty
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	12/2009

Abstract:

1) To study HIV-1 DNA vaccine by blocking the PD-1/PD-L interaction and by promoting in vivo antigen targeting to dendritic cells (year 1-1.5); 2) To study vaccinia-based HIV-1 vaccine by blocking the PD-1/PD-L interaction and by promoting in vivo antigen targeting at dendritic cells (year 1.5-3).

Project Title:	Characterization of novel anti-HIV/TB natural product analogues
Investigator(s):	Chen Z
Department:	Medical Faculty
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	03/2010

Abstract:

To understand the functional characeristics of a novel class of anti-HIV/TB natural products, which are essential for the identification of new drugs for the treatment of AIDS and TB patients

List of Research Outputs

Chen Z., Journal of Acquired Immune Deficiency Syndromes (IF: 4.5; Member of Editorial Board). Lippincott Williams & Wilkins, 2010.

Chen Z., Academic Editor, PLoS ONE. USA, Public Library of Science, 2010.

Chen Z., An effective heterologous mucosal prime intramuscular boost vaccine regimen against pathogenic SIVmac239 challenge, AIDS Vaccine 2009, Paris, France; October 19-23, 2009 Role: Poster presenter, and an invited speaker at IAVI's "Live Vaccine Vector" section . 2009.

Chen Z., Characterization of a Replication-competent Modified Vaccinia Tian Tan (MVTT) as a Vaccine Vector”, 2nd Annual World Summit of Antivirals, July 18-20, 2009.

Chen Z., Control of a pathogenic SIVmac239 infection by a heterologous mucosal prime and intramuscular boost vaccination strategy , 17 April 2010 Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting Role: Keynote Speaker . 2010.

Chen Z., HIV/AIDS Research at HKU AIDS Institute, 上海巴斯德研究所愛滋病專題學術研討會, Shanghai, China March 17-19, 2010 Role: Speaker . 2010.

Chen Z., HIV/AIDS Research at HKU-AIDS Institute, Cross Strait Workshop on Emerging Infectious Diseases, Xiamen, China September 17-19, 2009. 2009.

Chen Z., How to promote regional collaboration on HIV/AIDS research, AIDS meeting at Zhongshan Health Bureau, Zhongshan, China; March 20, 2010 Role: Speaker . 2010.

Chen Z., Is a mucosal AIDS vaccine possible? , May 11-14, 2010 China AIDS Vaccine Initiative (CAVI) Executive Committee Meeting & 2nd China AIDS Vaccine Forum, Shanghai, China Role: Speaker Co-organized by Vaccine Enterprise, NIH, WHO. 2010.

Chen Z., Opportunities and challenges in AIDS Research, May 27, 2010 深圳巿繼續教育學習班《2010深圳巿愛滋病篩查實驗室品質考評工作培訓班》, organized by Shenzhen CDC, Shenzhen, China Role: Keynote Speaker . 2010.

Chen Z., Progress report on AIDS mucosal vaccine development, China AIDS Vaccine Initiative (CAVI) / International AIDS Vaccine Initiative (IAVI) 2009 中國愛滋病疫苗工作會議, Beijing, China November 9-10, 2009 Role: Speaker . 2009.

Chen Z., Recent progress on anti-HIV treatment, April 24, 2010 深圳巿繼續教育學習班《愛滋病抗病毒治療的新進展》, organized by Shenzhen Third People’s Hospital, Shenzhen, China Role: Keynote Speaker . 2010.

Chen Z., Regional collaboration on HIV/AIDS, Shenzhen Center for Disease Control and Prevention(CDC), Shenzhen, China; January 27, 2010 Role: Speaker . 2010.

Chen Z., The Development of an AIDS Mucosal Vaccine, 3rd Ditan International Conference on Infectious Diseases; July 30 - August 2, 2009.

Chen Z., The Ongoing Research of an Effective AIDS Vaccine, Frontiers in Biomedical Research, HKU Li Ka Shing Faculty of Medicine December 4, 2009. 2009.

Chen Z. and Tang X., The development of an AIDS mucosal vaccine., In: Tang X. and Chen Z., Viruses. 2010, 2(1): 283-297.

Chen Z., The role of HKU AIDS institute in vaccine research, China AIDS Vaccine Initiative (CAVI) Executive Committee Meeting, Beijing, China; January 11-12, 2010 Role: CAVI ExCo member and invited speaker . 2010.

Liu H., Wang H., Yu W., Zhu W. and Chen Z., The route of inoculation determines the tissue tropism of modified vaccinia Tiantan expressing the spike glycoprotein of SARS-CoV in mice., J. Med. Virol.. 2010, 82(5): 727-734.

Lu X. and Chen Z., The development of anti-HIV-1 drugs, ACTA Pharmaceutica Sinica. 2010, 45(2): 165-176.

Vasan S., Schlesinger S.J. and Chen Z., Phase 1 Safety and Immunogenicity Evaluation of ADMVA, a Multigenic, DNA-based Clade C/B' HIV-1 Candidate Vaccine., PLoS ONE. 2010, 5(1): e8816.

Vasan S., Schlesinger S.J., Huang Y., Hurley A., Lombardo A. and Chen Z., Phase I Safety and Immunogenicity Evaluation of ADVAX, a Multigenic, DNA-based Clade C/B' HIV-1 Candidate Vaccine., PLoS ONE. 2010, 5(1): e8617.

Xu L., Zhang Y.F., Liu Y., Chen Z., Deng H., Ma Z., Wang H., Hu Z. and Deng F., Angiotensin-converting enzyme 2 (ACE2) from raccoon dog can serve as an efficient receptor for the spike protein of severe acute respiratory syndrome coronavirus., JGV. 2009, 90: 2695-2703.

Yu W., Fang Q., Zhu W., Wang H., Tien P., Zhang L. and Chen Z., One time intranasal vaccination with a modified vaccinia Tiantan strain MVTT (ZCI) protects animals against pathogenic viral challenge., Vaccine. 2010, 28(9): 2088-96.

Researcher : Cheng VCC

List of Research Outputs

Chen H., Cheung C.L., Tai H., Zhao P., Chan J.F.W., Cheng V.C.C., Chan K.H. and Yuen K.Y., Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus, Hong Kong, China, Emerg Infect Dis.. 2009, 15: 1970-2.

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Cheng V.C.C., Tai J.W.M., Wong L.M.W., Chan J.F.W., Li W.S., To K.K.W., Hung I.F.N., Chan K.H., Ho P.L. and Yuen K.Y., Prevention of nosocomial transmission of swine-origin pandemic influenza virus A/H1N1 by infection control bundle. , J Hosp Infect 2010. 2010, 74: 271-7.

Leung P.H.M., Chen J.H.K., Wong K.H., Chan K.C., Lam H.Y., Cheng V.C.C., Yuen K.Y. and Yam W.C., High prevalence of primary Enfuvirtide (ENF) resistance-associated mutations in HIV-1-infected patients in Hong Kong, Journal of Clinical Virology. 2010, 47: 273-275.

Li W.S., Chan K.H., To K.K.W., Wong S.S.Y., Ho P.L., Lau S.K.P., Woo P.C.Y., Tsoi H.W., Chan J.F.W., Cheng V.C.C., Zheng B., Chen H. and Yuen K.Y., Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses, Journal of Clinical Virology. 2009, 46: 325-330.

Li W.S., Hung I.F.N., To K.K.W., Chan K.H., Wong S.S.Y., Chan J.F.W., Cheng V.C.C., Tsang O.T., Lai S.T., Lau Y.L. and Yuen K.Y., The natural viral load profile of patients with pandemic swine-origin influenza A H1N1 2009 (pH1N1) and the effect of oseltamivir treatment., Chest. 2010, 137: 759-768.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Lau C.Y., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection, Clin Infect Dis.. 2010, 50: 850-859.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection, Clinical Infectious Disease. 2010, 50: 850-9.

To K.K.W., Wong S.S.Y., Cheng V.C.C., Tang S.F., Li W.S., Chan J.F.W., Seto W.K., Tse H. and Yuen K.Y., Epidemiology and clinical features of Shewanella infection over an eight-year period., Scandinavian journal of infectious diseases. 2010.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 Influenza A virus, Journal of Medical Virology. 2010, 82: 1-7.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Hung I.F.N., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 influenza A virus, J Med Virol. 2010, 82: 1-7.

Woo P.C.Y., Lau S.K.P., Ngan H.Y., Tung T.K., Leung S.Y., To K.K.W., Cheng V.C.C. and Yuen K.Y., Lichtheimia hongkongensis sp. nov., a novel Lichtheimia spp. associated with rhinocerebral, gastrointestinal and cutaneous mucormycosis, Diagnostic Microbiology and Infectious Disease. 2010, 66: 274-284.

Woo P.C.Y., Leung S.Y., To K.K.W., Chan J.F.W., Ngan H.Y., Cheng V.C.C., Lau S.K.P. and Yuen K.Y., Internal transcribed spacer region sequence heterogeneity in Rhizopus microsporus: implications on molecular diagnosis in clinical microbiology laboratories, Journal of Clinical Microbiology. 2010, 48: 208-214.

Researcher : Cheung CL

List of Research Outputs

Chen H., Cheung C.L., Tai H., Zhao P., Chan J.F.W., Cheng V.C.C., Chan K.H. and Yuen K.Y., Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus, Hong Kong, China, Emerg Infect Dis.. 2009, 15: 1970-2.

Dhanasekaran V., Poon L.L.M., Zhu H., Ma S.K., Li O.T.W., Cheung C.L., Smith G.J., Peiris J.S.M. and Guan Y., Reassortment of pandemic H1N1/2009 influenza A virus in swine., Science. 2010, 328: 1529.

Poon L.L.M., Mak W.Y., Li O.T.W., Chan K.H., Cheung C.L., Ma S.K., Yen H., Dhanasekaran V., Guan Y. and Peiris J.S.M., Rapid Detection of Reassortment of Pandemic H1N1/2009 Influenza Virus, Clinical Chemistry. 2010, 56: 1340-4.

Researcher : Cheung CL

List of Research Outputs

Researcher : Cheung CY

Project Title:	Determination of cellular receptors involved in differentially high pro-inflammatory induction by influenza A subtype H5N1 viruses in primary human monocyte-derived macrophages
Investigator(s):	Cheung CY
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	09/2006

Abstract:

The pandemic threat posted by avian influenza A H5N1 remains the major infectious disease threat currently confronting humankind. This virus is entrenched in poultry across a wide geographical distribution across Asia and continues to cause human disease. Although transmission to humans is inefficient at present, human disease tends to be severe with mortality rates reportedly in excess of 30%. Dissemination of the virus beyond the respiratory tract probably accounts for some of this unusual disease severity with recent H5N1 viruses. In addition, our previous studies suggest that, in contrast to conventional human influenza virus subtypes H1N1 or H3N2, the H5N1 viruses associated with human disease selectively hyper-induce pro-inflammatory cytokines from primary human macrophages (1). These include TNF alpha, IP-10, MIP1-alpha and RANTES. There is evidence that human patients with H5N1 disease have elevated levels of cytokines in their serum (2). H5N1 viruses have continued to evolve and reassort (3) and not all H5N1 virus genotypes are equally efficient at hyper-inducing the pro-inflammatory cytokines in vitro, the virus genotypes causing human disease in 1997, 2003 (see ref 4) and 2004 (unpublished data) being the most potent in this regard. The macrophages are a key sentinel cell of the immune system and an important source of pro-inflammatory cytokines, the respiratory epithelial cells are the key primary target of the influenza virus. We have therefore carried out preliminary studies on primary human bronchial and alveolar epithelial cells and find that the H5N1 virus genotypes associated with human disease hyper-induce a range of chemokines and cytokines including IP-10 and RANTES (Chan et al – in preparation). In contrast to macrophages, TNF alpha is not induced in these latter cells. Interestingly, both human (eg subtype H1N1) and avian (e.g. H5N1) viruses replicate equally efficiently in primary human respiratory epithelial cells and macrophages in vitro, a surprising observation given the supposedly different receptor preferences of avian and human viruses. The interaction and collaboration between toll-like receptors and other innate immune receptors is being increasingly recognized and the H5N1 – macrophage system would provide an excellent model in which to investigate these phenomena (5). The objectives of the present study are to define the mechanisms underlying this differential hyper-induction of cytokines by H5N1 viruses from primary human macrophages in vitro. Specifically we aim to compare human and avian viruses that are high and low cytokine inducers in vitro, in order to define viral receptors associated with innate immune sensing and virus entry in macrophages. References: 1) Cheung CY, Poon LL, Lau AS, Luk W, Lau YL, Shortridge KF, Gordon S, Guan Y, Peiris JS. Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease? Lancet. 2002 Dec 7;360(9348):1831-7. 2) Peiris JS, Yu WC, Leung CW, Cheung CY, Ng WF, Nicholls JM, Ng TK, Chan KH, Lai ST, Lim WL, Yuen KY, Guan Y. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet. 2004 Feb 21;363(9409):617-9. 3) Li KS, Guan Y, Wang J, Smith GJ, Xu KM, Duan L, Rahardjo AP, Puthavathana P, Buranathai C, Nguyen TD, Estoepangestie AT, Chaisingh A, Auewarakul P, Long HT, Hanh NT, Webby RJ, Poon LL, Chen H, Shortridge KF, Yuen KY, Webster RG, Peiris JS. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature. 2004 Jul 8;430(6996):209-13. 4) Guan Y, Poon LL, Cheung CY, Ellis TM, Lim W, Lipatov AS, Chan KH, Sturm-Ramirez KM, Cheung CL, Leung YH, Yuen KY, Webster RG, Peiris JS. H5N1 influenza: a protean pandemic threat. Proc Natl Acad Sci U S A. 2004 May 25;101(21):8156-61. 5) Mukhopadhyay S, Herre J, Brown GD, Gordon S. The potential for Toll-like receptors to collaborate with other innate immune receptors. Immunology. 2004 Aug;112(4):521-30.

Project Title:	Mechanism of action for the regulation of COX-2 dependent genes in human macrophages after infection with low and high pathogenic coronavirus and influenza viruses
Investigator(s):	Cheung CY, Lee MY
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2010

Abstract:

Refer to hard copy

List of Research Outputs

Cheung C.Y., Potential of the real-time and label-free cell sensor impedance technology to transform cell based infectivity assays for influenza viruses , Innovative Cell-Based Technologies in Public Health Hangzhou, Zhejiang, China. 2010.

Hui P.Y., Cheung C.Y., Lee M.Y., Leung C.K.L., Lai K.W. and Peiris J.S.M., The Role of p38 MAPK and Sensing Receptors in Highly-Pathogenic H5N1 Influenza Induced Cytokine Production, Cambridge Healthtech Institute's Eighth Annual Next-Gen Kinase Inhibitors - Oncology & Beyond . 2010.

Lee M.Y., Gardy J.L., Cheung C.Y., Cheung K.W., Hui P.Y., Ip N.Y., Guan Y., Hancock R.E. and Peiris J.S.M., Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages, PLoS One. 2009, 4(12): e8072.

Mok K.P., Wong C.H.K., Cheung C.Y., Chan M.C.W., Lee M.Y., Nicholls J.M., Guan Y. and Peiris J.S.M., Viral Genetic Determinants of H5N1 Influenza Viruses That Contribute to Cytokine Dysregulation, Journal of Infectious Diseases. 2009, 200(7): 1104-12.

Peiris J.S.M., Cheung C.Y., Leung C.Y.H. and Nicholls J.M., Innate immune responses to influenza A H5N1: friend or foe?, Trends in Immunology. 2009, 30(12): 574-84.

Researcher : Cheung KW

List of Research Outputs

Cheung K.W., Chin W.H., Chan K.H., Schumaker M., Mak W.Y., Leung S.Y.H., Wong A., Peiris J.S.M., Petrauskene O.V. and Poon L.L.M., Evaluation of novel H1N1-specific primer-probe sets using commercial RT-PCR mixtures and a premixed reaction stored in a lyophilized format, Journal of Virological Methods. 2010, 165: 302-4.

Lee M.Y., Gardy J.L., Cheung C.Y., Cheung K.W., Hui P.Y., Ip N.Y., Guan Y., Hancock R.E. and Peiris J.S.M., Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages, PLoS One. 2009, 4(12): e8072.

Researcher : Cheung PPH

List of Research Outputs

Cheung P.P.H., Leung C.Y.H., Chow C.K., Ng C.F., Tsang C.L., Wu Y.O., Ma S.K., Sia S.F., Guan Y. and Peiris J.S.M., Identifying The Species-origin Of Faecal Droppings Used For Avian Influenza Virus Surveillance In Wild-birds., J Clin Virol. 2009, 46(1): 90-93.

Researcher : Chin WH

List of Research Outputs

Cheung K.W., Chin W.H., Chan K.H., Schumaker M., Mak W.Y., Leung S.Y.H., Wong A., Peiris J.S.M., Petrauskene O.V. and Poon L.L.M., Evaluation of novel H1N1-specific primer-probe sets using commercial RT-PCR mixtures and a premixed reaction stored in a lyophilized format, Journal of Virological Methods. 2010, 165: 302-4.

Researcher : Choi KY

List of Research Outputs

Lau S.K.P., Li K.S.M., Huang Y., Shek C.T., Tse H., Wang M., Choi K.Y., Xu H., Lam S.F., Guo R., Chan K.H., Zheng B., Woo P.C.Y. and Yuen K.Y., Ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndrome-related Rhinolophus bat coronavirus in China reveal bats as a reservoir for acute, self-limiting infection that allows recombination events, Journal of Virology . 2010, 84: 2808-2819.

Woo P.C.Y., Lau S.K.P., Choi K.Y., Fung H.T., Shek K.C., Miao J., Chan B.Y.L., Ng K.H.L., Ngan H.Y., Ellis-Behnke R.G., Que T.L., Kam C.W. and Yuen K.Y., Resequencing microarray for detection of human adenoviruses in patients with conjunctivitis, Journal of Clinical Virology. 2010, 47: 282-285.

Researcher : Chow CK

List of Research Outputs

Cheung P.P.H., Leung C.Y.H., Chow C.K., Ng C.F., Tsang C.L., Wu Y.O., Ma S.K., Sia S.F., Guan Y. and Peiris J.S.M., Identifying The Species-origin Of Faecal Droppings Used For Avian Influenza Virus Surveillance In Wild-birds., J Clin Virol. 2009, 46(1): 90-93.

Chua T.H., Leung C.Y.H., Fang H.E., Chow C.K., Ma S.K., Sia S.F., Ng I.H.Y., Fenwick S.G., James C.M., Chua S.B., Chew S.T., Kwang J., Peiris J.S.M. and Trevor M.E., Evaluation Of A Subunit H5 Vaccine And An Inactivated H5n2 Avian Influenza Marker Vaccine In Ducks Challenged With Vietnamese H5n1 Highly Pathogenic Avian Influenza Virus, Influenza Research And Treatment. Hindawi Publishing Corporation, 2010, 2010.

Researcher : Chow KH

List of Research Outputs

Lo W.U., Ho P.L., Chow K.H., Lai E.L.Y., Yeung F. and Chiu S.S.S., Fecal carriage of CTXM type extended-spectrum beta-lactamase-producing organizms by children and their household contacts, Journal of Infection. 2010, 60: 286-292.

Researcher : Dai J

List of Research Outputs

Kao P.Y.P., Yang D., Lau L.S., Tsui H.W., Hu L., Dai J., Chan M.P., Chan C.M., Wang P., Zheng B., Sun J., Huang J., Madar J., Chen G., Chen H., Guan Y. and Yuen K.Y., Identification of Influenza a Nucleoprotein as an Antiviral Target, Nature Biotechnology. 2010, 28: 600-608.

Researcher : Dhanasekaran V

List of Research Outputs

Dhanasekaran V., Poon L.L.M., Zhu H., Ma S.K., Li O.T.W., Cheung C.L., Smith G.J., Peiris J.S.M. and Guan Y., Reassortment of pandemic H1N1/2009 influenza A virus in swine., Science. 2010, 328: 1529.

Guan Y., Dhanasekaran V., Bahl J., Zhu H., Wang J. and Smith G.J., The emergence of pandemic influenza viruses, Protein & Cell. 2010, 1: 9-13.

Poon L.L.M., Mak W.Y., Li O.T.W., Chan K.H., Cheung C.L., Ma S.K., Yen H., Dhanasekaran V., Guan Y. and Peiris J.S.M., Rapid Detection of Reassortment of Pandemic H1N1/2009 Influenza Virus, Clinical Chemistry. 2010, 56: 1340-4.

Smith G.J., Bahl J., Dhanasekaran V., Zhang J., Poon L.L.M., Chen H., Webster R.G., Peiris J.S.M. and Guan Y., Dating the emergence of pandemic influenza viruses, Proceedings of National Academic Science (USA). 2009, 106: 11709-11712.

Researcher : Du L

List of Research Outputs

Du L., Zhao G., Chan C.S., Li L., He Y., Zhou Y., Zheng B. and Jiang S., A 219-mer CHO-expressing RBD of SARS-CoV S protein induces potent immune responses and protective immunity. , Viral Immunol. . 2010, 23(2):: 211-219.

Du L., Zhao G., Li L., He Y., Zhou Y., Zheng B. and Jiang S., Antigenicity and immunogenicity of SARS-CoV S protein receptor-binding domain stably expressed in CHO cells., Biochem Biophys Res Commun . 2009, 384(4):: 486-90.

Du L., Zhao G., Chan C.S., Sun S., Chen M., Liu Z., Guo H., He Y., Zhou Y., Zheng B. and Jiang S., Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity. , Virology. 2009, 393:: 144-150.

Zhao G., Lin Y., Du L., Guan J., Sun S., Sui H., KOU Z., Chan C.S., Guo Y., Jiang S., Zheng B. and Zhou Y., An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses. 9. , Virol J.. 2010, 7(1):: 9.

Researcher : Du L

List of Research Outputs

Researcher : Duan L

List of Research Outputs

Zhu H., Li L., Duan L., Yip C.H. and Guan Y., Discovery of novel species of astrovirus, coronavirus and picornavirus in bats and co-infection of viruses from different families, Bats and Emerging Infectious Diseases Workshop. 2009.

Researcher : Fan YY

List of Research Outputs

Chan J.F.W., Lau S.K.P., Woo P.C.Y., Fan Y.Y., Ip J.J.K., Chan C.F., Luk J.K.H. and Yuen K.Y., Lactobacillus rhamnosus hepatic abscess associated with Mirizzi syndrome: a case report and review of the literature, Diagnostic Microbiology and Infectious Disease . 2010, 66: 94-97.

Lau S.K.P., Lee L.C.K., Fan Y.Y., Teng L.L., Tse C.W.S., Woo P.C.Y. and Yuen K.Y., Isolation of Laribacter hongkongensis, a novel bacterium associated with gastroenteritis, from Chinese tiger frog, International Journal of Food Microbiology. 2009, 129: 78-82.

Researcher : Fong JHM

List of Research Outputs

Chan M.C.W., Chan W.Y., Yu C.L., Ho C.C., Yuen K.M., Fong J.H.M., Tang L.L.S., Lai W.W.K., Lo A.C.Y., Chui W.H., Sihoe A.D.L., Kwong D.L.W., Tsao G.S.W., Poon L.L.M., Guan Y., Nicholls J.M. and Peiris J.S.M., Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract, American Journal of Pathology. 2010, 176(4): 1828-40.

Chan W.Y., Yu C.L., Yuen K.M., Fong J.H.M., Lo A.C.Y., Lai W.W.K., Wong D.S.H., Nicholls J.M., Peiris J.S.M. and Chan M.C.W., Infection of influenza A (H5N1) virus in human eye epithelium, an in vitro and ex vivo study , The 28th Annual Meeting of the American Society of Virology. 2009.

Researcher : Guan Y

Project Title:	Vaccines for the control of H5N1 and other avian influenza viruses
Investigator(s):	Guan Y
Department:	Microbiology
Source(s) of Funding:	The University of Hong Kong Foundation Seed Grant
Start Date:	04/2002

Abstract:

To study vaccines for the control of H5N1 and other avian influenza viruses.

Project Title:	Searching for the precursor of SARS-Cov in Southern China
Investigator(s):	Guan Y
Department:	Microbiology
Source(s) of Funding:	VCO SARS Research Fund
Start Date:	07/2003

Abstract:

To find source of SARS-Cov, and how this virus emerged in humans.

Project Title:	The role of migratory birds in the transmission of H5N1 Influenza virus in eastern Asia
Investigator(s):	Guan Y, Chen H, Smith GJ
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2007
Completion Date:	12/2009

Abstract:

To observe the epidemiology of influenza viruses of migratory birds in Southern China; to determine whether influenza viral gene pool in migratory birds contribute to generate novel reassortant H5N1 influenza viruses with pandemic potential; to investigate whether H5N1 influenza virus will become established in migratory bird fowls and result in further expansion of geographic distribution in Eurasian continent.

Project Title:	State Key Laboratory of Emerging Infectious Diseases
Investigator(s):	Guan Y
Department:	Microbiology
Source(s) of Funding:	Matching Fund for State Key Laboratory (SKL)
Start Date:	02/2009

Abstract:

State Key Laboratory of Emerging Infectious Diseases

Project Title:	Long-term surveillance for bat-borne viruses: An insight into viral ecology, evolutionary dynamics, and the source of zoonoses
Investigator(s):	Guan Y, Dhanasekaran V, Lai ACK, Zhu H
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2010

Abstract:

1) To further define the ecology and evolutionary pathway of Coronaviridae including SARS coronavirus: Evolutionary analysis of SARS-CoV revealed that there may be an unidentified intermediate host between bat and wild animal SARS-like viruses (Figure 1). Knowledge about maintenance and evolutionary dynamics of coronaviruses in bats is still incomplete. The mechanisms involved in interspecies transmissions from bats to other animals and the aspects associated with possible re-emergence of SARS in this region need to be further elucidated by long-term virological investigation; 2) To understand the prevalence and diversity of bat-borne Arenaviridae, Astroviridae, Bunyaviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, Picornaviridae, Reoviridae, Rhabdoviridae, and Togaviridae; The above virus families infect bats, humans and other animals and represent the most likely candidates to cause zoonoses. However little is known regarding their diversity and prevalence in a variety of bat species. Emergence of SARS-CoV showed that bat-borne virus continue to be introduced into humans via other animals, while other bat-borne viruses, such as Hendra and Nipah viruses, continually emerged and caused disease outbreak in human in neighboring regions. Also, the prevalence and diversity of these “emerged” bat-borne viruses have not been investigated in this region. The ability to identify potential zoonotic viruses (both in bat and other animals) that pose significant public health risk should be established through systematic surveillance; 3) To understand the ecology and evolutionary dynamics of bat-borne viruses and gain insights into the role of bats in the maintenance and transmission of potential emerging viruses Understanding the ecology, evolution and interspecies transmission of the above bat-borne viruses and the role of bats in facilitating diseases emergence is essential for disease prevention and only can be achieved through virological investigation. In particular, the recognition of interspecies transmission events relies on the long-term systematic surveillance.

List of Research Outputs

Chan K.H., Lai S.T., Poon L.L.M., Guan Y., Yuen K.Y., Peiris J.S.M. and Peiris J.S.M., Analytical sensitivity of rapid influenza antigen detection tests for swine-origin influenza virus (H1N1). , J Clin Virol. . 2009, 45: 205-7.

Chan M.C.W., Chan W.Y., Yu C.L., Ho C.C., Chui W.H., Lo C.K., Yuen K.M., Guan Y., Nicholls J.M. and Peiris J.S.M., Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells, Respiratory Research. 2009, 10: 102.

Chan M.C.W., Chan W.Y., Yu C.L., Ho C.C., Yuen K.M., Fong J.H.M., Tang L.L.S., Lai W.W.K., Lo A.C.Y., Chui W.H., Sihoe A.D.L., Kwong D.L.W., Tsao G.S.W., Poon L.L.M., Guan Y., Nicholls J.M. and Peiris J.S.M., Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract, American Journal of Pathology. 2010, 176(4): 1828-40.

Chen H., Wang Y., Liu W., Zhang J., Dong B., Fan X., Jong M.D., Farrar J., Riley S., Smith G.J. and Guan Y., Serology survey of pandemic (H1N1) 2009 virus, Guangxi Province, China, Emerging Infectious Diseases. 2009, 15: 1849-50.

Chen Y., Xu F., Gui X., Yang K., Wu X., Zheng Q., Ge S., Yuan Q., Yeo A... .E...T..., Zhang J., Guan Y., Chen H. and Xia N., A rapid test for the detection of influenza A virus including pandemic influenza A/H1N1 2009, J Virol Methods. 2010, 167: 100-2.

Cheung P.P.H., Leung C.Y.H., Chow C.K., Ng C.F., Tsang C.L., Wu Y.O., Ma S.K., Sia S.F., Guan Y. and Peiris J.S.M., Identifying The Species-origin Of Faecal Droppings Used For Avian Influenza Virus Surveillance In Wild-birds., J Clin Virol. 2009, 46(1): 90-93.

Dhanasekaran V., Poon L.L.M., Zhu H., Ma S.K., Li O.T.W., Cheung C.L., Smith G.J., Peiris J.S.M. and Guan Y., Reassortment of pandemic H1N1/2009 influenza A virus in swine., Science. 2010, 328: 1529.

Fang Y., Rowe T., Leon A.J., Banner D., Danesh A., Xu L., Ran L., Bosinger S.E., Guan Y., Chen H., Cameron C.C., Cameron M.J. and Kelvin D.J., Characterization of in vivo Adjuvant Activity in Influenza-Vaccinated Ferrets, J Virol. 2010, 84: 8369-88.

Guan Y., Dhanasekaran V., Bahl J., Zhu H., Wang J. and Smith G.J., The emergence of pandemic influenza viruses, Protein & Cell. 2010, 1: 9-13.

Guan Y., Faculty Outstanding Research Output Award, Li Ka Shing Faculty of Medicine, The University of Hong Kong. 2010.

Guan Y., The spectrum of threat- H1N1, H5N1, HIV, TB, malaria; the animal link - zoonoses; development of treatment and prevention, The 2010 East-West Alliance Meeting. 2010.

Kao P.Y.P., Yang D., Lau L.S., Tsui H.W., Hu L., Dai J., Chan M.P., Chan C.M., Wang P., Zheng B., Sun J., Huang J., Madar J., Chen G., Chen H., Guan Y. and Yuen K.Y., Identification of Influenza a Nucleoprotein as an Antiviral Target, Nature Biotechnology. 2010, 28: 600-608.

Lee M.Y., Gardy J.L., Cheung C.Y., Cheung K.W., Hui P.Y., Ip N.Y., Guan Y., Hancock R.E. and Peiris J.S.M., Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages, PLoS One. 2009, 4(12): e8072.

Liu N., Wang G., Lee K.M., Guan Y., Chen H. and Cai Z., Mutations in influenza virus replication and transcription: detection of amino acid substitutions in hemagglutinin of an avian influenza virus (H1N1), FASEB J.. 2009, 23: 3377-82.

Mok K.P., Wong C.H.K., Cheung C.Y., Chan M.C.W., Lee M.Y., Nicholls J.M., Guan Y. and Peiris J.S.M., Viral Genetic Determinants of H5N1 Influenza Viruses That Contribute to Cytokine Dysregulation, Journal of Infectious Diseases. 2009, 200(7): 1104-12.

Poon L.L.M., Chan K.H., Smith G.J., Leung C.S.W., Guan Y., Yuen K.Y. and Peiris J.S.M., Molecular detection of a novel human influenza (H1N1) of pandemic potential by conventional and real-time quantitative RT-PCR assays., Clin Chem.. 2009, 55: 1555-8.

Poon L.L.M., Mak W.Y., Li O.T.W., Chan K.H., Cheung C.L., Ma S.K., Yen H., Dhanasekaran V., Guan Y. and Peiris J.S.M., Rapid Detection of Reassortment of Pandemic H1N1/2009 Influenza Virus, Clinical Chemistry. 2010, 56: 1340-4.

Smith G.J., Bahl J., Dhanasekaran V., Zhang J., Poon L.L.M., Chen H., Webster R.G., Peiris J.S.M. and Guan Y., Dating the emergence of pandemic influenza viruses, Proceedings of National Academic Science (USA). 2009, 106: 11709-11712.

Tu W., Mao H., Zheng J., Liu Y., Chiu S.S.S., Qin G., Chan P.L., Lam K.T., Guan J., Zhang L., Guan Y., Yuen K.Y., Peiris J.S.M. and Lau Y.L., Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus, Journal of Virology. 2010, 84(13): 6527-6535.

Xing Z., Harper R., Anunciacion J., Yang Z., Gao W., Qu B., Guan Y. and Cardona C.J., Host Immune and Apoptotic Responses to Avian Influenza Virus H9N2 in Human Tracheobronchial Epithelial Cells, Am J Respir Cell Mol Biol. 2010.

Zhang J., Zhang Z., Fan X., Liu Y., Wang J., Zheng Z., Chen R., Wang P., Song W., Chen H. and Guan Y., 2009 pandemic H1N1 influenza virus replicates in human lung tissues, J Infect Dis. 2010, 201: 1522-6.

Zhu H., Li L., Duan L., Yip C.H. and Guan Y., Discovery of novel species of astrovirus, coronavirus and picornavirus in bats and co-infection of viruses from different families, Bats and Emerging Infectious Diseases Workshop. 2009.

Zhu H., Wang J., Wang P., Song W., Zheng Z., Chen R., Guo K., Zhang T., Peiris J.S.M., Chen H. and Guan Y., Substitution of lysine at 627 position in PB2 protein does not change virulence of the 2009 pandemic H1N1 virus in mice, Virology. 2010, 401: 1-5.

Researcher : Ho CC

List of Research Outputs

Chan M.C.W., Chan W.Y., Yu C.L., Ho C.C., Chui W.H., Lo C.K., Yuen K.M., Guan Y., Nicholls J.M. and Peiris J.S.M., Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells, Respiratory Research. 2009, 10: 102.

Chan M.C.W., Chan W.Y., Yu C.L., Ho C.C., Yuen K.M., Fong J.H.M., Tang L.L.S., Lai W.W.K., Lo A.C.Y., Chui W.H., Sihoe A.D.L., Kwong D.L.W., Tsao G.S.W., Poon L.L.M., Guan Y., Nicholls J.M. and Peiris J.S.M., Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract, American Journal of Pathology. 2010, 176(4): 1828-40.

Chan W.Y., Yuen K.M., Yu C.L., Ho C.C., Nicholls J.M., Peiris J.S.M. and Chan M.C.W., Differential Viral Replication Kinetics And Host Innate Immune Responses By Influenza A (H5N1) Virus In Human Bronchial Epithelial Cells At Different Differentiation Stages, The 28th Annual meeting of American Society for Virology. 2009.

Chan W.Y., Yuen K.M., Yu C.L., Ho C.C., Nicholls J.M., Peiris J.S.M. and Chan M.C.W., Influenza H5n1 And H1n1 Virus Replication And Innate Immune Responses In Bronchial Epithelial Cells Are Influenced By The State Of Differentiation, PLoS One. 2010, 5 (1): e8713.

Researcher : Ho PL

Project Title:	A phenotypic and genotypic analysis of vancomycin tolerance in Streptococcus pnemoniae
Investigator(s):	Ho PL, Yuen KY, Que TL
Department:	Microbiology
Source(s) of Funding:	Low Budget High Impact Programme
Start Date:	11/2000

Abstract:

To identify the frequency of occurrence of vancomycin tolerance in Streptococcus pneumoniae; to identify novel mutations in the histdine kinase (vncS) of tolerant pneumococci.

Project Title:	Molecular epidemiology of fluoroquinolone-resistant streptococcus pneumoniae in Hong kong and Canada
Investigator(s):	Ho PL
Department:	Microbiology
Source(s) of Funding:	Low Budget High Impact Programme
Start Date:	11/2001

Abstract:

To define the molecular epidemiology of fluoroquinolone-resistant strains of S. pneumoniae isolated in Hong Kong and Canada.

Project Title:	Risk factors for SARS in health care workers following incubation of SARS patients
Investigator(s):	Ho PL, Hung CT
Department:	Microbiology
Source(s) of Funding:	VCO SARS Research Fund
Start Date:	07/2003

Abstract:

To identify factors associated with SARS transmission in HCW who participated in intubation of SARS patients; to define the transmission probability of an intubation procedure of SARS patient and to describe the intubation procedural practice of clinicians in the first two months of the outbreak.

Project Title:	Fluoroquinolone susceptibility clinical breakpoints and fluoroquinolone-resistant determining mutations among clinical strains of streptococcus pneumoniae
Investigator(s):	Ho PL, Wong SSY
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To determine the frequency of occurrence of first step fluoroquinolone-resistant determining mutations among isolates categorized as susceptible by the currently accepted clinical breakpoints.

Project Title:	Evaluation of molecular tests for the rapid detection of rifampicin and isoniazid resistance in Mycobacterium tuberculosis and their impact on patient management
Investigator(s):	Ho PL, Yam WC, Leung CC, Yew WW, Mok YW, Chan KS, Tam CM
Department:	Microbiology
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	04/2006

Abstract:

(1) to evaluate rapid tests for genotypic detection of rifampicin and isoniazid resistance in Mycobacterium tuberculosis in respiratory specimens and culture isolates; (2) to assess the effects of a model for targeted testing of patients with risks for multidrug-resistant tuberculosis on patient management

List of Research Outputs

Chan G.C.F., Chan S., Ho P.L. and Ha S.Y., Effects of chelators (Deferoxamine, deferiprone and deferasirox) on the growth of klebsiella pneumoniae and aeromonas hydrophila isolated from transfusion-dependent thalassaemia patients., Hemoglobin (Proceedings of the 17th International Conference on Chelation (ICOC), Shenzhen, PR China 23-27 November 2007). 2009, 33(5): 352-360.

Chan G.C.F., Chan S., Ho P.L. and Ha S.Y., Effects of chelators (Desferal, Deferiprone & Deferaairox) on the growth of klebsiella and aeromonas isolated from transfusion dependent thalassaemia patients., Joint Annual Scientific Meeting, The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association Ltd. 28 November. 2009.

Chan G.C.F., Chan S., Ho P.L. and Ha S.Y., Effects of chelators (desferal, deferiprone & deferasirox) on the growth of Klebsiella and Aeromonas isolated from transfusion dependent thalassemia patients., Hemoglobin. 2009, 33(5): 352-360.

Cheng V.C., Yam W.C., Chan J.F., To K.K.W., Ho P.L. and Yuen K.Y., Clostridium difficile ribotype 027 arrives in Hong Kong, International Journal of Antimicrobial agents. UK, 2009, 34(5): 492-493.

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Cheng V.C.C., Tai J.W.M., Wong L.M.W., Chan J.F.W., Li W.S., To K.K.W., Hung I.F.N., Chan K.H., Ho P.L. and Yuen K.Y., Prevention of nosocomial transmission of swine-origin pandemic influenza virus A/H1N1 by infection control bundle. , J Hosp Infect 2010. 2010, 74: 271-7.

Ho P.L., Chief Executive's Commendation for Community Service, 2009, 行政長官社區服務獎狀, Chief Executive's Commendation for Community Service, 2009. 2009.

Lau S.K.P., Wong G.K.M., Poon R.W.S., Lee L.C.K., Leung K.W., Tse C.W.S., Ho P.L., Que T.L., Woo P.C.Y. and Yuen K.Y., Susceptibility Patterns Of Clinical And Fish Isolates Of Laribacter Hongkongensis: Comparison Of The Etest, Disc Diffusion And Broth Microdilution Methods, Journal Of Antimicrobial Chemotherapy. 2009, 63: 704-708.

Lau W.T., Ho P.L., Kao R.Y.T., Siu K.H., Cheng V.C., Yuen K.Y. and Yam W.C., Rapid diagnosis of multidrug-resistant smear-positive pulmonary tuberculosis, International Journal of Antimicrobial agents. UK, 2010, 35(2): 202-203.

Leung C.C., Yam W.C., Yew W.W., Ho P.L., Tam C.M., Law W.S., Au K.F. and Tsui P.W., T-Spot.TB Outperforms Tuberculin Skin Test in Predicting Tuberculosis Disease. , American Journal of respiratory and Critical Care medicine . 2010, 182(6): 834-40.

Li W.S., Chan K.H., To K.K.W., Wong S.S.Y., Ho P.L., Lau S.K.P., Woo P.C.Y., Tsoi H.W., Chan J.F.W., Cheng V.C.C., Zheng B., Chen H. and Yuen K.Y., Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses, Journal of Clinical Virology. 2009, 46: 325-330.

Lo W.U., Ho P.L., Chow K.H., Lai E.L.Y., Yeung F. and Chiu S.S.S., Fecal carriage of CTXM type extended-spectrum beta-lactamase-producing organizms by children and their household contacts, Journal of Infection. 2010, 60: 286-292.

Researcher : Huang Y

List of Research Outputs

Lau S.K.P., Li K.S.M., Huang Y., Shek C.T., Tse H., Wang M., Choi K.Y., Xu H., Lam S.F., Guo R., Chan K.H., Zheng B., Woo P.C.Y. and Yuen K.Y., Ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndrome-related Rhinolophus bat coronavirus in China reveal bats as a reservoir for acute, self-limiting infection that allows recombination events, Journal of Virology . 2010, 84: 2808-2819.

Woo P.C.Y., Lau S.K.P., Lam S.F., Lai K.Y., Huang Y., Lee P., Luk G.S.M., Dyrting K.C., Chan K.H. and Yuen K.Y., Comparative Analysis Of Complete Genome Sequences Of Three Avian Coronaviruses Reveals A Novel Group 3c Coronavirus, Journal of Virology. 2009, 83: 908-917.

Woo P.C.Y., Lau S.K.P., Huang Y., Lam S.F., Poon R.W.S., Tsoi H.W., Lee P., Tse H., Chan A.S., Luk G. and Yuen K.Y., Comparative analysis of six genome sequences of three novel picornaviruses, turdiviruses 1, 2 and 3, in dead wild birds and proposal of two novel genera, Orthoturdivirus and Paraturdivirus, in Picornaviridae, The Journal of general virology. 2010.

Researcher : Hui PY

Project Title:	Cambridge Healthtech Institute's Eighth Annual Next-Gen Kinase Inhibitors - Oncology & Beyond The Role of p38 MAPK and Sensing Receptors in Highly-Pathogenic H5N1 Influenza Induced Cytokine Production
Investigator(s):	Hui PY
Department:	Microbiology
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	06/2010
Completion Date:	06/2010

Abstract:

N/A

List of Research Outputs

Hui P.Y., Cheung C.Y., Lee M.Y., Leung C.K.L., Lai K.W. and Peiris J.S.M., The Role of p38 MAPK and Sensing Receptors in Highly-Pathogenic H5N1 Influenza Induced Cytokine Production, Cambridge Healthtech Institute's Eighth Annual Next-Gen Kinase Inhibitors - Oncology & Beyond . 2010.

Lee M.Y., Gardy J.L., Cheung C.Y., Cheung K.W., Hui P.Y., Ip N.Y., Guan Y., Hancock R.E. and Peiris J.S.M., Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages, PLoS One. 2009, 4(12): e8072.

Peiris J.S.M., Hui P.Y., Yen H., Peiris J.S.M. and Yen H., Host response to influenza virus: protection versus immunopathology, In: Adolfo Garcia-Sastre and Philippe Sansonetti, Current Opinion in Immunology. 2010, 22: 475-481.

Researcher : Hung IFN

Project Title:	Harvesting convalescent plasma for hyperimmune intravenous globulin production: a multicentres, randomised double-blind controlled trial for treatment of patients with serious S-OIV H1N1 infection
Investigator(s):	Hung IFN, Chan KH, Liang RHS, Lai ST, Yuen KY
Department:	Medicine
Source(s) of Funding:	Commissioned Studies on Human Swine Influenza Research
Start Date:	08/2009

Abstract:

To collect and prepare hyperimmune intravenous immunoglobulins (H-IVIG) from patients recovered from S-OIV H1N1 infection and to treat patients with severe S-OIV H1N1 infection with the prepared S-OIV H-IVIG. Patients' clinical outcome and adverse effects from the H-IVIG would be compared to patients who received simple IVIG.

List of Research Outputs

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Lau C.Y., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection, Clin Infect Dis.. 2010, 50: 850-859.

Researcher : Im SWK

Project Title:	Investigation of community exposure to a novel coronavirus associated with SARS and herd immunity developed among healthy blood donors
Investigator(s):	Im SWK, Yam WC
Department:	Microbiology
Source(s) of Funding:	VCO SARS Research Fund
Start Date:	07/2003

Abstract:

To determine the exposure of the Hong Kong community to the novel coronavirus and the extent of herd immunity developed; to optimize a cost-effective protocol suitable for high throughput blood testing screening.

Researcher : Kao RYT

Project Title:	Mode of action of a lead anti-influenza compound identified by chemical genetics
Investigator(s):	Kao RYT
Department:	Microbiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2006

Abstract:

Based on the concept of chemical genetics and in conjunction with the high-throughput screening (HTS) technologies we have developed, we set out to establish a HTS-based chemical genetic platform for the identification of biologically active small molecule compounds that will perturb most, if not all, biological pathways involved in the pathogenesis of influenza A viruses in cellular models. Forward chemical genetics has been employed to identify small molecule compounds that will interfere with infectivity of human influenza A/WSN/33 (H1N1) in Madin-Darby canine kidney (MDCK) cells. Primary screening of the library has identified more than 1,000 compounds that can perturb the infectivity of H1N1 virus in cell-based assays. A sampling survey of 70 primary hits indicates that ~10% of the hits have EC50 (median effective concentration) at or below 10 microM [determined by MTT (3-[4,5-dimethylth-iazol-2-yl]-2,5-diphenyltetrazolium bromide) assay and PRA (plaque reduction assay)]. The result is in good agreement with the ones we obtained from our previously published SARS-CoV study. One particular lead compound FA5123 {[4-(2-Chloro-4-nitro-phenyl)-2-methyl-piperazin-1-yl]-[3-(2-chloro-phenyl)-5-methyl-isoxazol-4-yl]-methanone} has been identified (figure 1). FA5123 inhibits influenza A/WSN/33 (H1N1) in MDCK cells with an EC50 of 5 microM and TC50 (median toxicity concentration) > 1 mM [determined by MTT (3-[4,5-dimethylth-iazol-2-yl]-2,5-diphenyltetrazolium bromide)-based assay]. The molecular target of this isolated compound will be defined by isolation of mutant viruses resistant to this particular compound followed by identification of the mutated gene by sequencing of the mutant viral gene segments. It is not our major goal to produce ready-to-use, marketable antiviral agents from this study, for that is the job of the pharmaceutical companies. We are exploring novel strategies that can be employed to obtain biologically active novel small-molecule compounds (with defined molecular targets) that will have the potential of being developed to be novel anti-influenza therapeutics.

Project Title:	Cloning and characterization of Streptococcus pneumoniae methionine aminopeptidase: a potential target for antimicrobial therapies
Investigator(s):	Kao RYT
Department:	Microbiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2007

Abstract:

Objectives of the proposed project: Co- and post-translational modifications have long been recognized as essential steps for the maturation, regulation, and eventually degradation of proteins. Since protein synthesis begins at N-terminus with methionine or N-formyl methionine (initiator methionine), modification at this site becomes one of the earliest and most important steps determining the fate of the translating peptide. Methionine aminopeptidases (MetAPs), the enzymes responsible for the catalytic removal of the N-terminal methionine, are defined by their highly conserved substrate specificity dictated by the residue adjacent to the initiator methionine residue. Extensive biochemical and mutational studies have confirmed that if the second residue in the primary sequence is small and uncharged (e.g. Ala, Cys, Gly, Pro, Ser, Thr, or Val), the MetAPs will then catalytically cleave the N-terminal methionine residue. There are two classes of MetAPs, designated MetAP1 (type I) and MetAP2 (type II), and both are metalloenzymes that will cleave the N-terminal methionine if the second residue is small and uncharged. Type I enzymes are found in Eubacteria while type II enzymes are found in Archaea, and methionine aminopeptidases of both types are present in eukaryotes. As Eubacteria contain only one type of methionine aminopeptidase gene (map), it has been demonstrated that deletion of this gene from E. coli and Salmonella typhimurium is lethal. Yeast expresses both map1 and map2 genes. Deletion of either one is not lethal but deletion mutant of both map1 and map2 is nonviable, indicating that N-terminal methionine removal is an essential function in both bacteria and yeast. Its physiological importance has given rise to considerable interest among researchers to design antimicrobial inhibitors that specifically target this enzyme. Analysis of map gene in S. pneumoniae: Extensive in silico studies reveal that there is only one copy of map gene in S. pneumoniae and MetAPs in S. pneumoniae and in E.coli share 33% identity in amino acid sequence (figure 1). It is generally believed that the MetAP from S. pneumoniae will have the same enzymatic activity and specificity as the E.coli counterpart as all proposed active site residues and metal ion binding motifs are conserved in the two MetAPs, though this speculation has yet to be demonstrated experimentally. Recent advancements in synthetic organic chemistry, molecular biology, and informatics have made possible the use of large collections of small molecules (chemical libraries) to investigate protein/chemical interactions in vitro and in vivo (Kao et al. 2002, 2004; Degterev et al., 2001; Peterson et al., 2000; Mayer et al., 1999). The term "chemical genetics” has been coined to signify the use of chemicals to systematically perturb, and thus determine, the function of proteins in the same way that mutations are used in classical genetics. In forward chemical genetics, small molecules that induce altered phenotypes in cells or organisms are identified and their cellular targets will then be determined subsequently. In reverse chemical genetics, small molecules that interact with a known, purified protein are identified in vitro and their effects on cells or organisms will then be examined. I intend to clone the gene methionine aminopeptidase employ high-throughput screened (HTS) based reverse chemical genetics to identify small molecules that will have specific inhibitory effects on the S. pneumoniae MetAP-I (SpMetAP-I). Resulting specific inhibitors of SpMetAP-I will be tested in cell-based assays (Streptococcus pneumoniae, Staphylococcus aureus, and E. coli) to determine their in vivo antimicrobial effects. My objectives are to: 1. Clone the gene encoding methionine aminopeptidase in Streptococcus pneumoniae R6 strain in E. coli. 2. Over-express spMetAP in E.coli host and purify the recombinant protein to homogeneity. 3. Characterize the enzymatic properties of spMetAP. 4. Cary out pilot-scale HTS of small molecule inhibitor of spMetAP. 5. Test the inhibitory effects of the anti-spMetAP compounds on S. pneumoniae, S. aureus, and E.coli in cellular assays.

List of Research Outputs

Lau W.T., Ho P.L., Kao R.Y.T., Siu K.H., Cheng V.C., Yuen K.Y. and Yam W.C., Rapid diagnosis of multidrug-resistant smear-positive pulmonary tuberculosis, International Journal of Antimicrobial agents. UK, 2010, 35(2): 202-203.

Leung Y.L., Tsui Y.K., Kao R.Y.T., Masuda K., Chan D. and Cheung K.M.C., Identifying therapeutic chemical agents for intervertebral disc degeneration by high throughput screening, 55th Annual Meeting of the Orthopaedic Research Society, New Orleans, USA. 2010.

Tong W.Y.T., Liang Y.M., Tam V., Yip H.K., Kao R.Y.T., Cheung K.M.C., Yeung K.W.K. and Lam Y.W., Biochemical characterization of the cell-biomaterial interface by quantitative proteomics, Mol Cell Proteomics. 2010.

Tsui Y.K., Leung Y.L., Kao R.Y.T., Masuda K., Chan D. and Cheung K.M.C., Identifying therapeutic chemical agents for intervertebral disc degeneration by high throughput screening, 56th Annual Meeting of the Orthopaedic Research Society, New Orleans, Louisiana, March 6-9, 2010.

Tsui Y.K., Cheung K.M.C., Leung Y.L., Chan D. and Kao R.Y.T., Uncovering new compounds for treatment of interveretebral disc degeneration by chemical genetics, 2010.

Yeung C.Y., Leung K.Y., Yeung K.W.K., Kao R.Y.T., Chu P.K., Cheung K.M.C. and Luk K.D.K., Inhibition of metallic implant-related bacterial infections by novel water plasma surface treatment, 29th Annual Congress of the Hong Kong Orthopaedic Association, Hong Kong, November 28-29, 2009.

Yeung K.W.K., Cheung K.M.C., Luk K.D.K., Yeung C.Y., Kao R.Y.T. and Chu P.K., Antibacterial surface and method of fabrication. PCT Patent Application (No.: PCT/CN2010/000216) Filed: Feb 18, 2010., PCT Patent Application. 2010.

Yeung K.W.K., Cheung K.M.C., Luk K.D.K., Yeung C.Y., Kao R.Y.T. and Chu P.K., Antibacterial surface and method of fabrication. U.S. Non-Provisional Patent (No.: 12/706,483). Filed: Feb 16, 2010., U.S. Non-Provisional Patent (No.: 12/706,483). Filed: Feb 16, 2010.. 2010.

Yeung K.W.K., Cheung K.M.C., Luk K.D.K., Yeung C.Y., Kao R.Y.T. and Chu P.K., Antibacterial surface and method of fabrication, PCT Patent Application (No.: PCT/CN2010/000216) filed 18 February 2010. 2010.

Yeung K.W.K., Cheung K.M.C., Luk K.D.K., Yeung C.Y., Kao R.Y.T. and Chu P.K., Antibacterial surface and method of fabrication, U.S. Non-Provisional Patent (No.: 12/706,483). filed 16 February 2010. 2010.

Yeung K.W.K., Leung K.Y., Kao R.Y.T., Chu P.K., Yip K., Luk K.D.K. and Cheung K.M.C., Feasibility Study of a New Plasma Coating to Suppress Bacterial Adhesion in Orthopaedic, Proceedings 4th International Conference on Technological Advances of Thin Films and Surface Coatings (ThinFilms 2008) (July 13-16, 2008). 2009, (Paper 4150) 35.

Yeung K.W.K., Kao R.Y.T., Chu P., Luk K.D.K. and Cheung K.M.C., Oxygen Plasma Implanted Titanium Surface to Resist Staphylococcus Aureus Adhesion., 22nd European Conference on Biomaterials (ESB2009), Lausanne, Switzerland, 7-11Sep 2009. Oral presentation.. 2009.

Researcher : Lai ELY

List of Research Outputs

Lo W.U., Ho P.L., Chow K.H., Lai E.L.Y., Yeung F. and Chiu S.S.S., Fecal carriage of CTXM type extended-spectrum beta-lactamase-producing organizms by children and their household contacts, Journal of Infection. 2010, 60: 286-292.

Researcher : Lai KW

List of Research Outputs

Hui P.Y., Cheung C.Y., Lee M.Y., Leung C.K.L., Lai K.W. and Peiris J.S.M., The Role of p38 MAPK and Sensing Receptors in Highly-Pathogenic H5N1 Influenza Induced Cytokine Production, Cambridge Healthtech Institute's Eighth Annual Next-Gen Kinase Inhibitors - Oncology & Beyond . 2010.

Researcher : Lai KY

List of Research Outputs

Woo P.C.Y., Lau S.K.P., Lam S.F., Lai K.Y., Huang Y., Lee P., Luk G.S.M., Dyrting K.C., Chan K.H. and Yuen K.Y., Comparative Analysis Of Complete Genome Sequences Of Three Avian Coronaviruses Reveals A Novel Group 3c Coronavirus, Journal of Virology. 2009, 83: 908-917.

Researcher : Lam HY

List of Research Outputs

Leung P.H.M., Chen J.H.K., Wong K.H., Chan K.C., Lam H.Y., Cheng V.C.C., Yuen K.Y. and Yam W.C., High prevalence of primary Enfuvirtide (ENF) resistance-associated mutations in HIV-1-infected patients in Hong Kong, Journal of Clinical Virology. 2010, 47: 273-275.

Researcher : Lam SF

List of Research Outputs

Lau S.K.P., Li K.S.M., Huang Y., Shek C.T., Tse H., Wang M., Choi K.Y., Xu H., Lam S.F., Guo R., Chan K.H., Zheng B., Woo P.C.Y. and Yuen K.Y., Ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndrome-related Rhinolophus bat coronavirus in China reveal bats as a reservoir for acute, self-limiting infection that allows recombination events, Journal of Virology . 2010, 84: 2808-2819.

Woo P.C.Y., Lau S.K.P., Lam S.F., Lai K.Y., Huang Y., Lee P., Luk G.S.M., Dyrting K.C., Chan K.H. and Yuen K.Y., Comparative Analysis Of Complete Genome Sequences Of Three Avian Coronaviruses Reveals A Novel Group 3c Coronavirus, Journal of Virology. 2009, 83: 908-917.

Woo P.C.Y., Lau S.K.P., Huang Y., Lam S.F., Poon R.W.S., Tsoi H.W., Lee P., Tse H., Chan A.S., Luk G. and Yuen K.Y., Comparative analysis of six genome sequences of three novel picornaviruses, turdiviruses 1, 2 and 3, in dead wild birds and proposal of two novel genera, Orthoturdivirus and Paraturdivirus, in Picornaviridae, The Journal of general virology. 2010.

Researcher : Lam TH

List of Research Outputs

Lam T.H., Cheng P.S., Lai S.T., Tsang T.Y., Cheng V.C.C., Ho S.L. and Yam W.C., Evaluation of in-house and commercial genotyping assays for molecular typing of hepatitis C virus in Hong Kong, BRITISH JOURNAL OF BIOMEDICAL SCIENCE. UK, 2010, 67(2): 82-84.

Researcher : Lau CY

List of Research Outputs

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Lau C.Y., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection, Clin Infect Dis.. 2010, 50: 850-859.

Woo P.C.Y., Tung T.K., Chan K.H., Lau C.Y., Lau S.K.P. and Yuen K.Y., Cytokine profiles induced by the novel swine-origin influenza A/H1N1 virus: implications for treatment strategies, Journal of Infectious Diseases. 2010, 201: 346-353.

Researcher : Lau CY

List of Research Outputs

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Lau C.Y., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection, Clin Infect Dis.. 2010, 50: 850-859.

Researcher : Lau LS

List of Research Outputs

Kao P.Y.P., Yang D., Lau L.S., Tsui H.W., Hu L., Dai J., Chan M.P., Chan C.M., Wang P., Zheng B., Sun J., Huang J., Madar J., Chen G., Chen H., Guan Y. and Yuen K.Y., Identification of Influenza a Nucleoprotein as an Antiviral Target, Nature Biotechnology. 2010, 28: 600-608.

Researcher : Lau SKP

Project Title:	The role of bats in the origin of severe acute respiratory syndrome coronavirus
Investigator(s):	Lau SKP, Woo PCY, Yuen KY
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	07/2007

Abstract:

To determine the epidemiology and ecology of SARS-CoV-like viruses and other coronaviruses in wild bats in Hong Kong and Guangdong, China; to study the phylogenetic relationship and molecular evolution of SARS-CoV-like viruses and other coronaviruses in bats; to investigate for possible recombination events between SARS-CoV-like viruses and other coronaviruses responsible for generation of SARS-CoV that infected civets and humans; to study the receptor binding domain of the spike protein of SARS-CoV-like viruses in bats and possible events leading to a spike protein capable of using palm civet and human ACE2.

Project Title:	Clinical and molecular epidemiology of human bocavirus in respiratory and fecal samples from children in Hong Kong
Investigator(s):	Lau SKP, Woo PCY, Yuen KY
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	10/2007

Abstract:

The objective of this study is to characterize the clinical and molecular epidemiology of human bocavirus in respiratory and fecal samples from children in Hong Kong

Project Title:	Genotyping of bat coronavirus HKU9, a novel bat coronavirus identified in Hong Kong
Investigator(s):	Lau SKP, Woo PCY, Yuen KY
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	09/2009

Abstract:

The objective of this study is to characterize the genotypes of a novel bat coronavirus, bat coronavirus HKU9 (bat-CoV HKU9), identified in Hong Kong. The complete RdRp, spike and nucleocapsid genes of different strains of bat-CoV HKU9 will be sequenced and analyzed for existence of multiple genotypes and potential recombination events.

Project Title:	The role of a novel rhinovirus species, rhinovirus C, in respiratory illness and its molecular epidemiology
Investigator(s):	Lau SKP, Tse H, Woo PCY, Yuen KY
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2010

Abstract:

1) To study the role of HRV-C in respiratory illness in humans and its clinical spectrum of disease and epidemiology; 2) To develop RT-PCR and serological tests for the diagnosis of HRV-C infection; 3) To study the molecular epidemiology of this novel rhinovirus species.

List of Research Outputs

Chan C.M., Lau S.K.P., Woo P.C.Y., Tse H., Zheng B., Chen L., Huang J. and Yuen K.Y., Identification Of Major Histocompatibility Complex Class I C Molecule As An Attachment Factor That Facilitates Coronavirus Hku1 Spike-mediated Infection, Journal of Virology. 2009, 83: 1026-1035.

Chan J.F.W., Lau S.K.P., Woo P.C.Y., Fan Y.Y., Ip J.J.K., Chan C.F., Luk J.K.H. and Yuen K.Y., Lactobacillus rhamnosus hepatic abscess associated with Mirizzi syndrome: a case report and review of the literature, Diagnostic Microbiology and Infectious Disease . 2010, 66: 94-97.

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Lau S.K.P., Yip C.Y., Lin A.W., Lee R.A., So L.Y., Lau Y.L., Chan K.H., Woo P.C.Y. and Yuen K.Y., Clinical and molecular epidemiology of human rhinovirus C in children and adults in Hong Kong reveals a possible distinct human rhinovirus C subgroup, Journal of Infectious Diseases. 2009, 200(7): 1096-1103.

Lau S.K.P., Chan K.H., Yip C.Y., Ng T.K., Tsang O.T., Woo P.C.Y. and Yuen K.Y., Confirmation of the first Hong Kong case of human infection by novel swine origin influenza A (H1N1) virus diagnosed using ultrarapid, real-time reverse transcriptase PCR, Journal of Clinical Microbiology. 2009, 47: 2344-2346.

Lau S.K.P., Discovery and characterization of novel coronaviruses. , Diagnosis and Research for Emerging Viral Infections. (Chang Gung University, Taipei) . 2009.

Lau S.K.P., Li K.S.M., Huang Y., Shek C.T., Tse H., Wang M., Choi K.Y., Xu H., Lam S.F., Guo R., Chan K.H., Zheng B., Woo P.C.Y. and Yuen K.Y., Ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndrome-related Rhinolophus bat coronavirus in China reveal bats as a reservoir for acute, self-limiting infection that allows recombination events, Journal of Virology . 2010, 84: 2808-2819.

Lau S.K.P., Yip C.Y., Woo P.C.Y. and Yuen K.Y., Human rhinovirus C: a newly discovered human rhinovirus species, Emerging Health Threats Journal. 2009, 3: e2.

Lau S.K.P., Woo P.C.Y., Wong B.H.L., Wong Y.P., Tsoi H.W., Wang M., Lee P., Xu H., Poon R.W.S., Guo R., Li K.S.M., Chan K.H., Zheng B. and Yuen K.Y., Identification and complete genome analysis of three novel paramyxoviruses, Tuhoko virus 1, 2 and 3, in fruit bats from China, Virology. 2010, 404: 106-116.

Lau S.K.P., Lee L.C.K., Fan Y.Y., Teng L.L., Tse C.W.S., Woo P.C.Y. and Yuen K.Y., Isolation of Laribacter hongkongensis, a novel bacterium associated with gastroenteritis, from Chinese tiger frog, International Journal of Food Microbiology. 2009, 129: 78-82.

Lau S.K.P., Wong G.K.M., Poon R.W.S., Lee L.C.K., Leung K.W., Tse C.W.S., Ho P.L., Que T.L., Woo P.C.Y. and Yuen K.Y., Susceptibility Patterns Of Clinical And Fish Isolates Of Laribacter Hongkongensis: Comparison Of The Etest, Disc Diffusion And Broth Microdilution Methods, Journal Of Antimicrobial Chemotherapy. 2009, 63: 704-708.

Li W.S., Chan K.H., To K.K.W., Wong S.S.Y., Ho P.L., Lau S.K.P., Woo P.C.Y., Tsoi H.W., Chan J.F.W., Cheng V.C.C., Zheng B., Chen H. and Yuen K.Y., Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses, Journal of Clinical Virology. 2009, 46: 325-330.

Tong S., Singh J., Ruone S., Humphrey C., Yip C.Y., Lau S.K.P., Anderson L.J. and Kaur T., Identification of adenoviruses in fecal specimens from wild chimpanzees (Pan trogylodytes schweinfurthii) in western Tanzania, The American Journal of Tropical Medicine and Hygiene. 2010, 82: 967-970.

Tse H., Tsoi H.W., Leung A.S.P., Lau S.K.P., Woo P.C.Y. and Yuen K.Y., Complete genome sequence of Staphylococcus lugdunensis strain HKU09-01, Journal of Bacteriology. 2010, 192: 1471-1472.

Woo P.C.Y., Lau S.K.P., Ngan H.Y., Tung T.K., Leung S.Y., To K.K.W., Cheng V.C.C. and Yuen K.Y., Lichtheimia hongkongensis sp. nov., a novel Lichtheimia spp. associated with rhinocerebral, gastrointestinal and cutaneous mucormycosis, Diagnostic Microbiology and Infectious Disease. 2010, 66: 274-284.

Woo P.C.Y., Lin A.W.C., Lau S.K.P. and Yuen K.Y., Acupuncture transmitted infections, British Medical Journal. 2010, 340: 1151-1152.

Woo P.C.Y., Lau S.K.P., Lam S.F., Lai K.Y., Huang Y., Lee P., Luk G.S.M., Dyrting K.C., Chan K.H. and Yuen K.Y., Comparative Analysis Of Complete Genome Sequences Of Three Avian Coronaviruses Reveals A Novel Group 3c Coronavirus, Journal of Virology. 2009, 83: 908-917.

Woo P.C.Y., Lau S.K.P., Huang Y., Lam S.F., Poon R.W.S., Tsoi H.W., Lee P., Tse H., Chan A.S., Luk G. and Yuen K.Y., Comparative analysis of six genome sequences of three novel picornaviruses, turdiviruses 1, 2 and 3, in dead wild birds and proposal of two novel genera, Orthoturdivirus and Paraturdivirus, in Picornaviridae, The Journal of general virology. 2010.

Woo P.C.Y., Tung T.K., Chan K.H., Lau C.Y., Lau S.K.P. and Yuen K.Y., Cytokine profiles induced by the novel swine-origin influenza A/H1N1 virus: implications for treatment strategies, Journal of Infectious Diseases. 2010, 201: 346-353.

Woo P.C.Y., Lau S.K.P. and Yuen K.Y., First Report Of Methicillin-resistant Staphylococcus Aureus Septic Arthritis Complicating Acupuncture: Simple Procedure Resulting In Most Devastating Outcome, Diagnostic Microbiology And Infectious Disease. 2009, 63: 92-95.

Woo P.C.Y., Fong A.H.C., Ngan H.Y., Tam D.M.W., Teng L.L., Lau S.K.P. and Yuen K.Y., First Report Of Tsukamurella Keratitis: Association Between T. Tyrosinosolvens And T. Pulmonia And Ophthalmologic Infections, Journal Of Clinical Microbiology. 2009, 47: 1953-1956.

Woo P.C.Y., Teng L.L., Lam K.K.M., Tse C.W.S., Leung K.W., Leung A.W.S., Lau S.K.P. and Yuen K.Y., First report of Gordonibacter pamelaeae bacteremia, Journal of Clinical Microbiology . 2010, 48: 319-322.

Woo P.C.Y., Teng L.L., Wu J.K.L., Leung F.P.S., Tse H., Fung A.M.Y., Lau S.K.P. and Yuen K.Y., Guidelines for interpretation of 16S rRNA gene sequence-based results for identification of medically important aerobic Gram-positive bacteria., Journal of Medical Microbiology. 2009, 58: 1030-6.

Woo P.C.Y., Leung S.Y., To K.K.W., Chan J.F.W., Ngan H.Y., Cheng V.C.C., Lau S.K.P. and Yuen K.Y., Internal transcribed spacer region sequence heterogeneity in Rhizopus microsporus: implications on molecular diagnosis in clinical microbiology laboratories, Journal of Clinical Microbiology. 2010, 48: 208-214.

Woo P.C.Y., Wong S.S.Y., Teng L.L., Leung K.W., Ngan H.Y., Zhao D., Tse H., Lau S.K.P. and Yuen K.Y., Leptotrichia hongkongensis sp. nov., a novel Leptotrichia species with the oral cavity as its natural reservoir, Journal of Zhejiang University-SCIENCE B. 2010, 11: 391-401.

Woo P.C.Y., Lau S.K.P., Choi K.Y., Fung H.T., Shek K.C., Miao J., Chan B.Y.L., Ng K.H.L., Ngan H.Y., Ellis-Behnke R.G., Que T.L., Kam C.W. and Yuen K.Y., Resequencing microarray for detection of human adenoviruses in patients with conjunctivitis, Journal of Clinical Virology. 2010, 47: 282-285.

Yap D.Y.H., Lau S.K.P., Lamb S., Choy C.B.Y., Chan D.T.M., Lai K.N. and Tang S.C.W., An unusual organism for PD-related peritonitis: Hafnia alvei, Peritoneal Dialysis International. 2010, 30(2): 254-255.

Yip C.Y., Lau S.K.P., Zhou B., Zhang M.X., Tsoi H.W., Chan K.H., Chen X.C., Woo P.C.Y. and Yuen K.Y., Emergence of enterovirus 71 "double-recombinant" strains belonging to a novel genotype D originating from southern China: first evidence for combination of intratypic and intertypic recombination events in EV71., Archives of Virology. 2010.

Researcher : Lau WT

List of Research Outputs

Lau W.T., Ho P.L., Kao R.Y.T., Siu K.H., Cheng V.C., Yuen K.Y. and Yam W.C., Rapid diagnosis of multidrug-resistant smear-positive pulmonary tuberculosis, International Journal of Antimicrobial agents. UK, 2010, 35(2): 202-203.

Researcher : Lee MY

Project Title:	Direct identification and quantification of host and viral microRNAs after influenza infection using the next generation ultra-high throughput DNA sequencer
Investigator(s):	Lee MY, Lok S, Cheung CY
Department:	Microbiology
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	05/2009

Abstract:

To characterize and compare the microRNA transcriptomes of pathogenic H5N1 or common H1N1 influenza virus infected human macrophages to help derived a regulatory network that aid the identification of pathogenic determinants and to discover novel host and viral microRNA after influenza infection using the next generation ultra-high throughput DNA sequencer.

List of Research Outputs

Hui P.Y., Cheung C.Y., Lee M.Y., Leung C.K.L., Lai K.W. and Peiris J.S.M., The Role of p38 MAPK and Sensing Receptors in Highly-Pathogenic H5N1 Influenza Induced Cytokine Production, Cambridge Healthtech Institute's Eighth Annual Next-Gen Kinase Inhibitors - Oncology & Beyond . 2010.

Lee M.Y., Gardy J.L., Cheung C.Y., Cheung K.W., Hui P.Y., Ip N.Y., Guan Y., Hancock R.E. and Peiris J.S.M., Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages, PLoS One. 2009, 4(12): e8072.

Mok K.P., Wong C.H.K., Cheung C.Y., Chan M.C.W., Lee M.Y., Nicholls J.M., Guan Y. and Peiris J.S.M., Viral Genetic Determinants of H5N1 Influenza Viruses That Contribute to Cytokine Dysregulation, Journal of Infectious Diseases. 2009, 200(7): 1104-12.

Researcher : Lee P

List of Research Outputs

Lau S.K.P., Woo P.C.Y., Wong B.H.L., Wong Y.P., Tsoi H.W., Wang M., Lee P., Xu H., Poon R.W.S., Guo R., Li K.S.M., Chan K.H., Zheng B. and Yuen K.Y., Identification and complete genome analysis of three novel paramyxoviruses, Tuhoko virus 1, 2 and 3, in fruit bats from China, Virology. 2010, 404: 106-116.

Woo P.C.Y., Lau S.K.P., Lam S.F., Lai K.Y., Huang Y., Lee P., Luk G.S.M., Dyrting K.C., Chan K.H. and Yuen K.Y., Comparative Analysis Of Complete Genome Sequences Of Three Avian Coronaviruses Reveals A Novel Group 3c Coronavirus, Journal of Virology. 2009, 83: 908-917.

Woo P.C.Y., Lau S.K.P., Huang Y., Lam S.F., Poon R.W.S., Tsoi H.W., Lee P., Tse H., Chan A.S., Luk G. and Yuen K.Y., Comparative analysis of six genome sequences of three novel picornaviruses, turdiviruses 1, 2 and 3, in dead wild birds and proposal of two novel genera, Orthoturdivirus and Paraturdivirus, in Picornaviridae, The Journal of general virology. 2010.

Researcher : Leung ASP

List of Research Outputs

Tse H., Tsoi H.W., Leung A.S.P., Lau S.K.P., Woo P.C.Y. and Yuen K.Y., Complete genome sequence of Staphylococcus lugdunensis strain HKU09-01, Journal of Bacteriology. 2010, 192: 1471-1472.

Researcher : Leung CKL

List of Research Outputs

Hui P.Y., Cheung C.Y., Lee M.Y., Leung C.K.L., Lai K.W. and Peiris J.S.M., The Role of p38 MAPK and Sensing Receptors in Highly-Pathogenic H5N1 Influenza Induced Cytokine Production, Cambridge Healthtech Institute's Eighth Annual Next-Gen Kinase Inhibitors - Oncology & Beyond . 2010.

Researcher : Leung CSW

List of Research Outputs

Poon L.L.M., Chan K.H., Smith G.J., Leung C.S.W., Guan Y., Yuen K.Y. and Peiris J.S.M., Molecular detection of a novel human influenza (H1N1) of pandemic potential by conventional and real-time quantitative RT-PCR assays., Clin Chem.. 2009, 55: 1555-8.

Researcher : Leung CYH

List of Research Outputs

Cheung P.P.H., Leung C.Y.H., Chow C.K., Ng C.F., Tsang C.L., Wu Y.O., Ma S.K., Sia S.F., Guan Y. and Peiris J.S.M., Identifying The Species-origin Of Faecal Droppings Used For Avian Influenza Virus Surveillance In Wild-birds., J Clin Virol. 2009, 46(1): 90-93.

Chua T.H., Leung C.Y.H., Fang H.E., Chow C.K., Ma S.K., Sia S.F., Ng I.H.Y., Fenwick S.G., James C.M., Chua S.B., Chew S.T., Kwang J., Peiris J.S.M. and Trevor M.E., Evaluation Of A Subunit H5 Vaccine And An Inactivated H5n2 Avian Influenza Marker Vaccine In Ducks Challenged With Vietnamese H5n1 Highly Pathogenic Avian Influenza Virus, Influenza Research And Treatment. Hindawi Publishing Corporation, 2010, 2010.

Lau E.H.Y., Leung C.Y.H. and Peiris J.S.M., The role of drinking water as a transmission route of influenza (H9N2) in live poultry market (poster presentation), Epidemics² Second International Conference on Infectious Diseases Dynamics, 2-4 December 2009, Athens, Greece. Athens, Elsevier, 2009, P2.17.

Peiris J.S.M., Cheung C.Y., Leung C.Y.H. and Nicholls J.M., Innate immune responses to influenza A H5N1: friend or foe?, Trends in Immunology. 2009, 30(12): 574-84.

Researcher : Leung SY

List of Research Outputs

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Woo P.C.Y., Lau S.K.P., Ngan H.Y., Tung T.K., Leung S.Y., To K.K.W., Cheng V.C.C. and Yuen K.Y., Lichtheimia hongkongensis sp. nov., a novel Lichtheimia spp. associated with rhinocerebral, gastrointestinal and cutaneous mucormycosis, Diagnostic Microbiology and Infectious Disease. 2010, 66: 274-284.

Woo P.C.Y., Leung S.Y., To K.K.W., Chan J.F.W., Ngan H.Y., Cheng V.C.C., Lau S.K.P. and Yuen K.Y., Internal transcribed spacer region sequence heterogeneity in Rhizopus microsporus: implications on molecular diagnosis in clinical microbiology laboratories, Journal of Clinical Microbiology. 2010, 48: 208-214.

Researcher : Leung SYH

List of Research Outputs

Cheung K.W., Chin W.H., Chan K.H., Schumaker M., Mak W.Y., Leung S.Y.H., Wong A., Peiris J.S.M., Petrauskene O.V. and Poon L.L.M., Evaluation of novel H1N1-specific primer-probe sets using commercial RT-PCR mixtures and a premixed reaction stored in a lyophilized format, Journal of Virological Methods. 2010, 165: 302-4.

Researcher : Li KSM

List of Research Outputs

Lau S.K.P., Li K.S.M., Huang Y., Shek C.T., Tse H., Wang M., Choi K.Y., Xu H., Lam S.F., Guo R., Chan K.H., Zheng B., Woo P.C.Y. and Yuen K.Y., Ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndrome-related Rhinolophus bat coronavirus in China reveal bats as a reservoir for acute, self-limiting infection that allows recombination events, Journal of Virology . 2010, 84: 2808-2819.

Lau S.K.P., Woo P.C.Y., Wong B.H.L., Wong Y.P., Tsoi H.W., Wang M., Lee P., Xu H., Poon R.W.S., Guo R., Li K.S.M., Chan K.H., Zheng B. and Yuen K.Y., Identification and complete genome analysis of three novel paramyxoviruses, Tuhoko virus 1, 2 and 3, in fruit bats from China, Virology. 2010, 404: 106-116.

Researcher : Li L

List of Research Outputs

Zhu H., Li L., Duan L., Yip C.H. and Guan Y., Discovery of novel species of astrovirus, coronavirus and picornavirus in bats and co-infection of viruses from different families, Bats and Emerging Infectious Diseases Workshop. 2009.

Researcher : Li OTW

List of Research Outputs

Dhanasekaran V., Poon L.L.M., Zhu H., Ma S.K., Li O.T.W., Cheung C.L., Smith G.J., Peiris J.S.M. and Guan Y., Reassortment of pandemic H1N1/2009 influenza A virus in swine., Science. 2010, 328: 1529.

Li O.T.W. and Poon L.L.M., One step closer to universal influenza epitopes., Expert Rev Anti Infect Ther.. 2009, 7: 687-90.

Poon L.L.M., Mak W.Y., Li O.T.W., Chan K.H., Cheung C.L., Ma S.K., Yen H., Dhanasekaran V., Guan Y. and Peiris J.S.M., Rapid Detection of Reassortment of Pandemic H1N1/2009 Influenza Virus, Clinical Chemistry. 2010, 56: 1340-4.

Researcher : Li WS

List of Research Outputs

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Cheng V.C.C., Tai J.W.M., Wong L.M.W., Chan J.F.W., Li W.S., To K.K.W., Hung I.F.N., Chan K.H., Ho P.L. and Yuen K.Y., Prevention of nosocomial transmission of swine-origin pandemic influenza virus A/H1N1 by infection control bundle. , J Hosp Infect 2010. 2010, 74: 271-7.

Li W.S., Chan K.H., To K.K.W., Wong S.S.Y., Ho P.L., Lau S.K.P., Woo P.C.Y., Tsoi H.W., Chan J.F.W., Cheng V.C.C., Zheng B., Chen H. and Yuen K.Y., Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses, Journal of Clinical Virology. 2009, 46: 325-330.

Li W.S., Hung I.F.N., To K.K.W., Chan K.H., Wong S.S.Y., Chan J.F.W., Cheng V.C.C., Tsang O.T., Lai S.T., Lau Y.L. and Yuen K.Y., The natural viral load profile of patients with pandemic swine-origin influenza A H1N1 2009 (pH1N1) and the effect of oseltamivir treatment., Chest. 2010, 137: 759-768.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Lau C.Y., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection, Clin Infect Dis.. 2010, 50: 850-859.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection, Clinical Infectious Disease. 2010, 50: 850-9.

To K.K.W., Wong S.S.Y., Cheng V.C.C., Tang S.F., Li W.S., Chan J.F.W., Seto W.K., Tse H. and Yuen K.Y., Epidemiology and clinical features of Shewanella infection over an eight-year period., Scandinavian journal of infectious diseases. 2010.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 Influenza A virus, Journal of Medical Virology. 2010, 82: 1-7.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Hung I.F.N., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 influenza A virus, J Med Virol. 2010, 82: 1-7.

Researcher : Lin Y

List of Research Outputs

Lin Y., Tanner J.A. and Zheng B., In vivo selection and characterization of DNA aptamers against H5N1 virus nucleoprotein. , European Congress of Clinical Microbiology and Infectious Diseases. Vienna, Austria. 2010.

Lin Y., Shum K.T., Tanner J.A. and Zheng B., Study of DNA aptamers binding H5N1 virus nucleoprotein. , Thailand Conference on Emerging Infectious and Neglected Diseases. Chonbrti, Thailand.. 2010.

Tanner J.A., Zheng B., Lin Y., Kimura M., Lui E.L.H. and Shum K.T., Selection, validation and delivery of DNA aptamers against infectious disease targets. , 5th Annual Meeting of the Oligonucleotide Therapeutics Society, Fukuoka, Japan . 2009.

Researcher : Lin Y

List of Research Outputs

Researcher : Lo WU

List of Research Outputs

Lo W.U., Ho P.L., Chow K.H., Lai E.L.Y., Yeung F. and Chiu S.S.S., Fecal carriage of CTXM type extended-spectrum beta-lactamase-producing organizms by children and their household contacts, Journal of Infection. 2010, 60: 286-292.

Researcher : Lu X

List of Research Outputs

Lu X. and Chen Z., The development of anti-HIV-1 drugs, ACTA Pharmaceutica Sinica. 2010, 45(2): 165-176.

Researcher : Ma SK

List of Research Outputs

Cheung P.P.H., Leung C.Y.H., Chow C.K., Ng C.F., Tsang C.L., Wu Y.O., Ma S.K., Sia S.F., Guan Y. and Peiris J.S.M., Identifying The Species-origin Of Faecal Droppings Used For Avian Influenza Virus Surveillance In Wild-birds., J Clin Virol. 2009, 46(1): 90-93.

Chua T.H., Leung C.Y.H., Fang H.E., Chow C.K., Ma S.K., Sia S.F., Ng I.H.Y., Fenwick S.G., James C.M., Chua S.B., Chew S.T., Kwang J., Peiris J.S.M. and Trevor M.E., Evaluation Of A Subunit H5 Vaccine And An Inactivated H5n2 Avian Influenza Marker Vaccine In Ducks Challenged With Vietnamese H5n1 Highly Pathogenic Avian Influenza Virus, Influenza Research And Treatment. Hindawi Publishing Corporation, 2010, 2010.

Cowling B.J., Chan K.H., Fang J., Lau L.L.H., So H.C., Fung R.O.P., Ma S.K., Kwong A.S.K., Chan C.W., Tsui W.W.S., Ngai H.Y., Chu D.W.S., Lee P.W.Y., Chiu M.C. and Leung G.M., Comparative epidemiology of pandemic and seasonal influenza A in households, New England Journal of Medicine. 2010, 362: 2175-2184.

Dhanasekaran V., Poon L.L.M., Zhu H., Ma S.K., Li O.T.W., Cheung C.L., Smith G.J., Peiris J.S.M. and Guan Y., Reassortment of pandemic H1N1/2009 influenza A virus in swine., Science. 2010, 328: 1529.

Garcia J., Pepin S., Lagarde N.J.C., Ma S.K., vogel F.R., Chan K.H., Chiu S.S.S. and Peiris J.S.M., Heterosubtype neutralizing responses to influenza A (H5N1) viruses are mediated by antibodies to virus haemagglutinin, PLoS One. 2009, 4(11): e7918.

Garcia J., Fries K., Lagarde N.J.C., Ma S.K., Buchy P., de Jong M.D. and Peiris J.S.M., Optimization and evaluation of an influenza A (H5) pseudotyped lentiviral particle – based serological assay. , Journal of clinical virology. 2010, 47: 29-33.

Poon L.L.M., Mak W.Y., Li O.T.W., Chan K.H., Cheung C.L., Ma S.K., Yen H., Dhanasekaran V., Guan Y. and Peiris J.S.M., Rapid Detection of Reassortment of Pandemic H1N1/2009 Influenza Virus, Clinical Chemistry. 2010, 56: 1340-4.

Researcher : Mak WY

List of Research Outputs

Cheung K.W., Chin W.H., Chan K.H., Schumaker M., Mak W.Y., Leung S.Y.H., Wong A., Peiris J.S.M., Petrauskene O.V. and Poon L.L.M., Evaluation of novel H1N1-specific primer-probe sets using commercial RT-PCR mixtures and a premixed reaction stored in a lyophilized format, Journal of Virological Methods. 2010, 165: 302-4.

Poon L.L.M., Mak W.Y., Li O.T.W., Chan K.H., Cheung C.L., Ma S.K., Yen H., Dhanasekaran V., Guan Y. and Peiris J.S.M., Rapid Detection of Reassortment of Pandemic H1N1/2009 Influenza Virus, Clinical Chemistry. 2010, 56: 1340-4.

Researcher : Miao J

List of Research Outputs

Woo P.C.Y., Lau S.K.P., Choi K.Y., Fung H.T., Shek K.C., Miao J., Chan B.Y.L., Ng K.H.L., Ngan H.Y., Ellis-Behnke R.G., Que T.L., Kam C.W. and Yuen K.Y., Resequencing microarray for detection of human adenoviruses in patients with conjunctivitis, Journal of Clinical Virology. 2010, 47: 282-285.

Researcher : Mok BWY

Project Title:	Dynamic of nucleo-cytoplasmic trafficking of ribonucleoproteins in influenza A viruses replication
Investigator(s):	Mok BWY, Chen H
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	10/2008

Abstract:

The genome of the Influenza virus has eight segmented RNAs of negative polarity. Each RNA segment has to bind to the viral ribonucleoprotein (vRNP) complexes in order to deliver into the nucleus of the infected cell for replication and expression. How the genetic materials are trafficked in and out of the nucleus is therefore of great importance for the understanding of viral replcaition. The translocation of genomic ribonucleoproteins (vRNPs) via the nucleus pore complexes of the infected cells is tightly regulated. During the early stage of the infection, the vRNPs are predominantly imported into the nucleus; in the late phase of the infection, i.e. prior to assembly into progeny virions, the newly synthesized RNPs are exported from the nucleus and accumulation in the cytoplasm, while the import of vRNP is inhibited. By far, only limited number of cellular factors have been identified that is involved in the nuclear transport of viral RNA polymerase complex/subunits, examples are importin-, Ran binding protein 5 (RanBP5), cellular chaperone hsp90, hsp70 and CRM1. Highly pathogenic H5N1 influenza virus is one of three subtypes of avian Influenza A viruses which have been found able to cause infection in humans and other mammal species. H5N1 influenza viruses have become endemic in poultry populations throughout Southeast Asia and continue to cause sporadic human infections with over 60% fatality rate. Although human-to-human transmission of these viruses has been relative rare, repeated incidence of human infection might initiate a new pandemic of the disease. Several determinants of host specificity and pathogenicity of Influenza A viruses have been identified, including that associated with receptor specificity, antigenic variability, proteolytic activation and replication rate. However, little is known regarding how the efficacy of nuclear targeting and translocation of the vRNPs, which may contribute to the host range adaptation and virulence of the Influenza A viruses. Nucleolus - a dynamic subnuclear organelle with roles in biogenesis and assembly of ribosome components - is another focus in this study. Until recently, the interaction between the RNA viruses and the nucleolus has become of interest. Although such interaction has been shown to arrogate host cells functions and viral replication, the research on this area is still in its infancy. This study will focus on the functional roles of nucleolar targeting and localization of the viral proteins in viral replication. The objectives of this project include: (1) To correlate the translocation efficiency of the vRNPs of influenza A subtypes with tissue and host specificity. For this purpose, time course study will be performed to compare both the nuclear import and export of the vRNPs of influenza A subtypes (e.g. avian influenza virus H5N1 or N9N2 and human influenza virus H1N1 or H3N2) in different cell lines of different host and tissue origins. (2) To study the influence of temperature variation on nucleocytoplasmic trafficking of vRNP in infected cells. (e.g. 33 °C vs 41 °C, representing the temperature at human upper respiratory tract and at avian intestinal tractm respectively). (3) Evaluation of novel cellular factors potentially involved in nucleocytoplasmic trafficking of viral RNP. Using mass spectrometry, a number of host factors interacting with the viral RNP were identified by our group recently. Potential candidates will be selected, and their roles involved in RNPs shuttling via the nuclear pore complex will be studied.

Researcher : Mok KP

List of Research Outputs

Lee D.C.W., Mok K.P., Law H.Y., Peiris J.S.M. and Lau A.S.Y., Differential replication of avian influenza H9N2 viruses in human alveolar epithelial A549 cells., Virol J. 2010, 7: 71.

Mok K.P., Wong C.H.K., Cheung C.Y., Chan M.C.W., Lee M.Y., Nicholls J.M., Guan Y. and Peiris J.S.M., Viral Genetic Determinants of H5N1 Influenza Viruses That Contribute to Cytokine Dysregulation, Journal of Infectious Diseases. 2009, 200(7): 1104-12.

Researcher : Ng CF

List of Research Outputs

Cheung P.P.H., Leung C.Y.H., Chow C.K., Ng C.F., Tsang C.L., Wu Y.O., Ma S.K., Sia S.F., Guan Y. and Peiris J.S.M., Identifying The Species-origin Of Faecal Droppings Used For Avian Influenza Virus Surveillance In Wild-birds., J Clin Virol. 2009, 46(1): 90-93.

Researcher : Ng F

List of Research Outputs

Zhou J., Huang J., Poon K.M., Chen D., Chan C.S., Ng F., Guan X.Y., Watt R.M., Lu L., Yuen K.Y. and Zheng B., Functional dissection of an IFN-alfa/belta receptor 1 promoter variant that confers higher risk to chronic hepatitis B virus infection. , J Hepat.. 2009, 51(2):: 322-332.

Researcher : Ng IHY

List of Research Outputs

Chua T.H., Leung C.Y.H., Fang H.E., Chow C.K., Ma S.K., Sia S.F., Ng I.H.Y., Fenwick S.G., James C.M., Chua S.B., Chew S.T., Kwang J., Peiris J.S.M. and Trevor M.E., Evaluation Of A Subunit H5 Vaccine And An Inactivated H5n2 Avian Influenza Marker Vaccine In Ducks Challenged With Vietnamese H5n1 Highly Pathogenic Avian Influenza Virus, Influenza Research And Treatment. Hindawi Publishing Corporation, 2010, 2010.

Researcher : Ng MH

List of Research Outputs

Ng M.H., Yuen K.Y. and Zheng B., Oral DNA Composition for HBV Chronic Infection. , 2009.

Researcher : Ng SP

Project Title:	Collection of background information on the alternative faecal indicators in the environmental waters of Hong Kong and their correlation with Escherichia coli
Investigator(s):	Ng SP, Yam WC
Department:	Microbiology
Source(s) of Funding:	Environment Protection Department - General Award
Start Date:	06/2001

Abstract:

To detect and enumerate alternative faecal microbial indicator organisms in the environmental waters of Hong Kong and to correlate the results with Escherichia coli in order to assess their value in water quality monitoring.

Researcher : Ngan HY

List of Research Outputs

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Woo P.C.Y., Lau S.K.P., Ngan H.Y., Tung T.K., Leung S.Y., To K.K.W., Cheng V.C.C. and Yuen K.Y., Lichtheimia hongkongensis sp. nov., a novel Lichtheimia spp. associated with rhinocerebral, gastrointestinal and cutaneous mucormycosis, Diagnostic Microbiology and Infectious Disease. 2010, 66: 274-284.

Woo P.C.Y., Fong A.H.C., Ngan H.Y., Tam D.M.W., Teng L.L., Lau S.K.P. and Yuen K.Y., First Report Of Tsukamurella Keratitis: Association Between T. Tyrosinosolvens And T. Pulmonia And Ophthalmologic Infections, Journal Of Clinical Microbiology. 2009, 47: 1953-1956.

Woo P.C.Y., Leung S.Y., To K.K.W., Chan J.F.W., Ngan H.Y., Cheng V.C.C., Lau S.K.P. and Yuen K.Y., Internal transcribed spacer region sequence heterogeneity in Rhizopus microsporus: implications on molecular diagnosis in clinical microbiology laboratories, Journal of Clinical Microbiology. 2010, 48: 208-214.

Woo P.C.Y., Wong S.S.Y., Teng L.L., Leung K.W., Ngan H.Y., Zhao D., Tse H., Lau S.K.P. and Yuen K.Y., Leptotrichia hongkongensis sp. nov., a novel Leptotrichia species with the oral cavity as its natural reservoir, Journal of Zhejiang University-SCIENCE B. 2010, 11: 391-401.

Woo P.C.Y., Lau S.K.P., Choi K.Y., Fung H.T., Shek K.C., Miao J., Chan B.Y.L., Ng K.H.L., Ngan H.Y., Ellis-Behnke R.G., Que T.L., Kam C.W. and Yuen K.Y., Resequencing microarray for detection of human adenoviruses in patients with conjunctivitis, Journal of Clinical Virology. 2010, 47: 282-285.

Researcher : Peiris JSM

Project Title:	IV International Symposium on Respiratory Viral Infections The Influenza Disease Burden in Hong Kong: the Rates of Hospitalisation in Children
Investigator(s):	Peiris JSM
Department:	Microbiology
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	11/2001

Abstract:

N/A

Project Title:	Influenza pandemic preparedness in Asia (Research collaboration with national Institute of Allergy and Infectious Diseases (NIAID), St. Jude Children's Research Hospital, Inc. (SJCRH) and The University of Hong Kong)
Investigator(s):	Peiris JSM, Guan Y
Department:	Microbiology
Source(s) of Funding:	National Institutes of Health, US Department of Health and Human Services - General Award
Start Date:	04/2003

Abstract:

To study influenza pandemic preparedness in Asia.

Project Title:	Virus-cell interaction and the pathogenesis of SARS
Investigator(s):	Peiris JSM
Department:	Microbiology
Source(s) of Funding:	VCO SARS Research Fund
Start Date:	07/2003

Abstract:

To explore what is the biological basis for the selective attraction of macrophages to the lung; to study what immunopathological consequences follow.

Project Title:	Viral determinants underlying the increased secretion of pro-inflammatory cytokines in H5N1 infected human macrophages: a mechanism for the unusual severity of human H5N1 disease?
Investigator(s):	Peiris JSM, Guan Y, Lau ASY, Poon LLM
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	09/2003

Abstract:

To identify the viral genetic determinants responsible for the differential cytokine hyper-induction associated with H5N1/97 viruses. We have already established the role of the viral NS gene, however, a role for other viral genes has not been excluded. we hypothesize (and have preliminary evidence) that one or more other viral genes are also involved in the hyper-induction of cytokines; to determine whether the avian viral genes/gene products of H5N1/97 directly up-regulate cytokine induction or lack "immune evasion" mechanisms evolved by human influenza viruses? to determine whether the differential up-regulation of cytokines associated with H5N1/97 is also observed in human lung epithelial cells (primary bronchial epithelial cells and human lung epithelial cell lines e.g. A549 cells.

Project Title:	The macrophage in the pathogenesis of Severe Acute Respiratory Syndrome Coronavirus infection
Investigator(s):	Peiris JSM
Department:	Microbiology
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	12/2005

Abstract:

The global gene expression profiling of SARS-CoV infected macrophages will provide the basis for a more detailed analysis of the signaling pathways involved in subsequent studies, and may provide rational and novel therapeutic options to be devised for treating SARS.

Project Title:	Mass Tag PCR: A novel, multiplex and potentially sensitive approach for the rapid detection of respiratory pathogens
Investigator(s):	Peiris JSM, Chiu SSS, Cheung CY
Department:	Microbiology
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	06/2006

Abstract:

To divise, optimize and evaluate the Mass Tag PCR system for the rapid disgnosis for simultaneous screening of a wide spectrum of causative agents for human respiratory tract infections, including the avian influenza H5N1 and H7N7, SARS-coronavirus (SARS-CoV). Thiw will significantly facilitate better prevention, treatment and control of infectious diseases.

Project Title:	The pathogenesis of avian influenza A H5N1 in humans: macrophage and epithelial cell-virus interactions in vitro and ex-vivo
Investigator(s):	Peiris JSM
Department:	Microbiology
Source(s) of Funding:	The Wellcome Trust - General Award
Start Date:	01/2007

Abstract:

Specific aims are to: 1) Characterise the influenza viral replication profiles in tissue explant (ex-vivo) cultures of nasopharyngeal biopsies and lung tissue and primary cell cultures of human macrophages and respiratory (nasopharyngeal, bronchial, alveolar) epithelium. 2) Charaterise the functional receptors for H5N1 virus on macrophages and nasopharyngeal epithelium. 3) Define the consequences of viral entry via alternative pathways including the entry of non-neutralised virus antibody complexes via the Fc and complement receptors, to determine how these pathways affects subsequent viral replication and /or innate immune responses such as cytokine/chemokine secretion.

Project Title:	Communicable Diseases Surveillance and Response (CSR) - Standardization and shipment of PCR diagnostic kit for Avian Influenza detection to Member countries (viz: Bangladesh, Indonesia, Myanmar, Sri Lanka and Thailand)
Investigator(s):	Peiris JSM
Department:	Microbiology
Source(s) of Funding:	Collaborating Project Fund
Start Date:	06/2007

Abstract:

To compile diagnostic reagents in the form of kits for RT-PCR detection of H5N1 influenza for the South East Asia Region countries on behalf of WHO / SEAR.

Project Title:	Control of Pandemic and Inter-pandemic Influenza
Investigator(s):	Peiris JSM, Guan Y, Yuen KY, Chen H, Leung GM, Lau YL
Department:	Microbiology
Source(s) of Funding:	Areas of Excellence Scheme
Start Date:	01/2008

Abstract:

nil

Project Title:	Effector roles of cytokine cascades in the pathogenesis of human H5N1 disease
Investigator(s):	Peiris JSM, Cheung CY, Lee MY, Nicholls JM
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2008

Abstract:

To investigate the effect of soluble mediators from H5N1 infected cells (macrophages, lung epithelium) in relation to the activation of secondary cytokines (viz. the secondary cytokine cascades), and the gene expression related to apoptosis, oxidative stress, nitric oxide and other stress / toxicity pathways; to investigate the effect of such soluble mediators in relation to the induction of an antiviral state.

List of Research Outputs

Buchy P., Vong S., Garcia J., Chu S., Hien T.T., Hien V.M., Channa M., Ha D.Q., Vinh Chau N.V., Simons C., Farrar J.J., Peiris J.S.M. and de Jong M.D., Kinetics of neutralizing antibodies in patients naturally infected by H5N1 virus. , PlosOne. 2010, 5: e10864.

Chan K.H., Lai S.T., Poon L.L.M., Guan Y., Yuen K.Y., Peiris J.S.M. and Peiris J.S.M., Analytical sensitivity of rapid influenza antigen detection tests for swine-origin influenza virus (H1N1). , J Clin Virol. . 2009, 45: 205-7.

Chan M.C.W., Chan W.Y., Yu C.L., Ho C.C., Chui W.H., Lo C.K., Yuen K.M., Guan Y., Nicholls J.M. and Peiris J.S.M., Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells, Respiratory Research. 2009, 10: 102.

Chan M.C.W., Chan W.Y., Yu C.L., Ho C.C., Yuen K.M., Fong J.H.M., Tang L.L.S., Lai W.W.K., Lo A.C.Y., Chui W.H., Sihoe A.D.L., Kwong D.L.W., Tsao G.S.W., Poon L.L.M., Guan Y., Nicholls J.M. and Peiris J.S.M., Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract, American Journal of Pathology. 2010, 176(4): 1828-40.

Chan W.Y., Chan M.C.W., Wong C.N., Karamanska R., Dell A., Haslam S.M., Sihoe A.D., Chui W.H., Triana-Baltzer G., Li Q., Peiris J.S.M., Fang F. and Nicholls J.M., DAS181 Inhibits H5N1 Influenza virus Infection of Human Lung Tissues., Antimicrobial Agents and Chemotherapy. 2009, 53(9): 3935-3941.

Chan W.Y., Yuen K.M., Yu C.L., Ho C.C., Nicholls J.M., Peiris J.S.M. and Chan M.C.W., Differential Viral Replication Kinetics And Host Innate Immune Responses By Influenza A (H5N1) Virus In Human Bronchial Epithelial Cells At Different Differentiation Stages, The 28th Annual meeting of American Society for Virology. 2009.

Chan W.Y., Yu C.L., Yuen K.M., Fong J.H.M., Lo A.C.Y., Lai W.W.K., Wong D.S.H., Nicholls J.M., Peiris J.S.M. and Chan M.C.W., Infection of influenza A (H5N1) virus in human eye epithelium, an in vitro and ex vivo study , The 28th Annual Meeting of the American Society of Virology. 2009.

Chan W.Y., Yuen K.M., Yu C.L., Ho C.C., Nicholls J.M., Peiris J.S.M. and Chan M.C.W., Influenza H5n1 And H1n1 Virus Replication And Innate Immune Responses In Bronchial Epithelial Cells Are Influenced By The State Of Differentiation, PLoS One. 2010, 5 (1): e8713.

Chan W.Y., Chan M.C.W., Nicholls J.M. and Peiris J.S.M., Tropism and host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract , XII International Symposium on Respiratory Viral Infections. 2010.

Cheng K.Y., Cowling B.J., Chan K.H., Fang J., Seto W.H., Yung R.W.H., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., Factors affecting QuickVue Influenza A + B rapid test performance in the community setting, Diagnostic Microbiology and Infectious Disease. 2009, 65(1): 35-41.

Cheung K.W., Chin W.H., Chan K.H., Schumaker M., Mak W.Y., Leung S.Y.H., Wong A., Peiris J.S.M., Petrauskene O.V. and Poon L.L.M., Evaluation of novel H1N1-specific primer-probe sets using commercial RT-PCR mixtures and a premixed reaction stored in a lyophilized format, Journal of Virological Methods. 2010, 165: 302-4.

Cheung P.P.H., Leung C.Y.H., Chow C.K., Ng C.F., Tsang C.L., Wu Y.O., Ma S.K., Sia S.F., Guan Y. and Peiris J.S.M., Identifying The Species-origin Of Faecal Droppings Used For Avian Influenza Virus Surveillance In Wild-birds., J Clin Virol. 2009, 46(1): 90-93.

Ching C.Y.J., Chan Y.K., Lee H.L.E., Xu M.S., Ting K.P., So T.M., Sham P.C., Leung G.M., Peiris J.S.M. and Khoo U.S., Significance of the myxovirus resistance A (MxA) gene -123C>a single-nucleotide polymorphism in suppressed interferon beta induction of severe acute respiratory syndrome coronavirus infection, J Infect Dis. 2010, 201(12): 1899-908.

Chiu S.S.S., Chan K.H., Chen H., Young B.W., Lim W., Wong W.H.S., Lau Y.L. and Peiris J.S.M., Virologically confirmed population-based burden of hospitalization caused by influenza A and B among children in Hong Kong, Clinical Infectious Diseases. 2009, 49: 1016-1021.

Chua T.H., Leung C.Y.H., Fang H.E., Chow C.K., Ma S.K., Sia S.F., Ng I.H.Y., Fenwick S.G., James C.M., Chua S.B., Chew S.T., Kwang J., Peiris J.S.M. and Trevor M.E., Evaluation Of A Subunit H5 Vaccine And An Inactivated H5n2 Avian Influenza Marker Vaccine In Ducks Challenged With Vietnamese H5n1 Highly Pathogenic Avian Influenza Virus, Influenza Research And Treatment. Hindawi Publishing Corporation, 2010, 2010.

Cowling B.J., Leung G.M., Riley S., Ip D.K.M., Chiu S.S.S., Peiris J.S.M. and Chan K.H., A randomized controlled trial of the effectiveness of FluMist® vaccine in school aged children to reduce infection and transmission of influenza in children and their households (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong. Hong Kong, School of Public Health/HKU, 2009, 21.

Cowling B.J., Chiu S.S.S., Chan K.H., Peiris J.S.M. and Leung G.M., A randomized controlled trial of the effectiveness of vaccinating children to reduce household transmission of influenza (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong. Hong Kong, School of Public Health/HKU, 2009, 20.

Cowling B.J., Chan K.H., Fang J., Cheng K.Y., Fung R.O.P., Lim Wai W.S., Sin J.W.F., Seto W.H., Yung R.W.H., Chu D.W.S., Chiu B., Lee P., Chiu M.C., Lee H.C., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., A randomized trial of face masks and hand hygiene to prevent influenza transmission in households (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong. Hong Kong, School of Public Health/HKU, 2009, 22.

Cowling B.J., Chan K.H., Fang J., Cheng K.Y., Fung R.O.P., Lim Wai W.S., Sin J.W.F., Seto W.H., Yung R.W.H., Chu D.W.S., Chiu B.C.F., Lee P.W.Y., Chiu M.C., Lee H.C., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., Facemasks and hand hygiene to prevent influenza transmission in households: a cluster randomized trial, Annals of Internal Medicine. 2009, 151(7): 437-446.

Dhanasekaran V., Poon L.L.M., Zhu H., Ma S.K., Li O.T.W., Cheung C.L., Smith G.J., Peiris J.S.M. and Guan Y., Reassortment of pandemic H1N1/2009 influenza A virus in swine., Science. 2010, 328: 1529.

Hui P.Y., Cheung C.Y., Lee M.Y., Leung C.K.L., Lai K.W. and Peiris J.S.M., The Role of p38 MAPK and Sensing Receptors in Highly-Pathogenic H5N1 Influenza Induced Cytokine Production, Cambridge Healthtech Institute's Eighth Annual Next-Gen Kinase Inhibitors - Oncology & Beyond . 2010.

Khoo U.S., Chan Y.K., Ching C.Y.J., Chan V.S.F., Ip Y.C., Yam L., Chu C.M., Lai S.T., So K.M., Wong T.Y., Chung P.H., Yip S.P., Sham P.C., Leung G.M., Lin C.L. and Peiris J.S.M., Functional role of ICAM-3 polymorphism in genetic susceptibility to SARS infection, Hong Kong Med Journal. 2009, 26-9.

Lai J.C.C., Chan W.W.L., Kien F.S., Nicholls J.M., Peiris J.S.M. and Garcia J., Formation of virus-like particles from human cell lines exclusively expressing Influenza neuraminidase, Journal of General Virology . 2010, 2322-30.

Lau E.H.Y., Leung C.Y.H. and Peiris J.S.M., The role of drinking water as a transmission route of influenza (H9N2) in live poultry market (poster presentation), Epidemics² Second International Conference on Infectious Diseases Dynamics, 2-4 December 2009, Athens, Greece. Athens, Elsevier, 2009, P2.17.

Lau L.L.H., Fang J., Chan K.H., Ma E., Leung G.M., Peiris J.S.M. and Cowling B.J., Homologous and heterologous immune responses to naturally-acquired influenza virus infection (poster presentation), 14th International Congress on Infectious Diseases, 9-12 March 2010, Miami, USA . Miami, USA, International Congress on Infectious Diseases, 2010, 77.

Lau L.L.H., Cowling B.J., Fang J., Chan K.H., Peiris J.S.M. and Leung G.M., The dynamics between viral shedding and the clinical course of natural influenza infections (Poster presentation), 14th Research Postgraduate Symposium, 2-3 December 2009, Hong Kong. Hong Kong, LKS Faculty of Medicine, HKU, 2009, 96.

Lau L.L.H., Cowling B.J., Fang J., Cheng K.Y., Chan K.H., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., The trajectories of viral shedding, clinical course and tympanic temperature in natural influenza infections (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong. Hong Kong, School of Public Health/HKU, 2009.

Lau L.L.H., Cowling B.J., Fang J., Chan K.H., Lau E.H.Y., Lipsitch M., Cheng K.Y., Houck P.M., Uyeki T.M., Peiris J.S.M. and Leung G.M., Viral shedding and clinical illness in naturally acquired influenza virus infections, Journal of Infectious Diseases. 2010, 201(10): 1509-1516.

Law H.Y., Lee D.C.W., Yuen K.Y., Peiris J.S.M. and Lau A.S.Y., Cellular response to influenza virus infection: a potential role for autophagy in CXCL10 and interferon-alpha induction and implications in pathogenesis., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Lee D.C.W., Mok K.P., Law H.Y., Peiris J.S.M. and Lau A.S.Y., Differential replication of avian influenza H9N2 viruses in human alveolar epithelial A549 cells., Virol J. 2010, 7: 71.

Lee M.Y., Gardy J.L., Cheung C.Y., Cheung K.W., Hui P.Y., Ip N.Y., Guan Y., Hancock R.E. and Peiris J.S.M., Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages, PLoS One. 2009, 4(12): e8072.

Leung G.M., Ho L.M., Lam T.H., Hedley A.J. and Peiris J.S.M., Prevalence of SARS-CoV antibody in all Hong Kong patient contacts, Hong Kong Medical Journal. 2009, 15(6) Suppl 9: S27-S29.

Mao H., Tu W., Qin G., Law H.K., Sia S.F., Chan P.L., Liu Y., Lam K.T., Zheng J., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, J Virol. 2009, 83(18): 9215-22.

Mao H., Tu W., Qin G., Lau H.K.W., Chan P.L., Liu Y., Lam K.T., Zhang Y., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, Journal of Virology. 2009, 83: 9215-9222.

Mao H., Tu W., Liu Y., Qin G., Zheng J., Chan P.L., Lam K.T., Peiris J.S.M. and Lau Y.L., Inhibition of human natural killer cell activity by influenza virions and hemagglutinin, Journal of Virology. 2010, 84: 4148-4157.

Mok K.P., Wong C.H.K., Cheung C.Y., Chan M.C.W., Lee M.Y., Nicholls J.M., Guan Y. and Peiris J.S.M., Viral Genetic Determinants of H5N1 Influenza Viruses That Contribute to Cytokine Dysregulation, Journal of Infectious Diseases. 2009, 200(7): 1104-12.

Ng S., Cowling B.J., Chan K.H., Chiu S.S.S., Peiris J.S.M. and Leung G.M., A randomized controlled trial of the effectiveness of vaccinating children to reduce household transmission of influenza (Poster presentation), 14th Research Postgraduate Symposium, 2-3 December 2009, Hong Kong. Hong Kong, LKS Faculty of Medicine, HKU, 2009, 86.

Ng S., Cowling B.J., Fang J., Chan K.H., Ip D.K.M., Cheng K.Y., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., Effects of oseltamivir treatment on duration of clinical illness and viral shedding and household transmission of influenza virus, Clinical Infectious Diseases. 2010, 50(5): 707-714.

Peiris J.S.M., "Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic" in Nature 2009;459:1122-5., Faculty Outstanding Research Output Award. 2010.

Peiris J.S.M., Tu W. and Yen H., A novel H1N1 virus causes the first pandemic of the 21^st century, European Journal of Immunology. 2009, 39: 2946-2954.

Peiris J.S.M., Chair of Sessions on Emerging Virus Diseases; Viruses at the Edge; Which Virus for which Disease; Novel H1N1 influenza: Late Breakers., ICAAC, San Francisco, U.S.A.. 2009.

Peiris J.S.M., Hui P.Y., Yen H., Peiris J.S.M. and Yen H., Host response to influenza virus: protection versus immunopathology, In: Adolfo Garcia-Sastre and Philippe Sansonetti, Current Opinion in Immunology. 2010, 22: 475-481.

Peiris J.S.M., Influenza A viral genetic determinants of cytokine hyper-induction in human macrophages., Supervisor of Ph.D. student Mr. Chris Mok Ka Pun.. 2009.

Peiris J.S.M., Cheung C.Y., Leung C.Y.H. and Nicholls J.M., Innate immune responses to influenza A H5N1: friend or foe?, Trends in Immunology. 2009, 30(12): 574-84.

Peiris J.S.M., Invited Lecture: Session: Overviews fo Lung Infury in Human Influenza; title "Comparison of disease spectrum and mechanisms of pathogenesis in H5N1 and pandemic H1N1 influenza., Mechanisms of Lung Injury and Immunomodulator Interventions in Influenza. Ventura, U.S.A.. 2010.

Peiris J.S.M., Invited lecture "Avian Influenza: ecology and molecular epidemiology"., AFCD Hong Kong. Animal Health Workshop on Avian Influenza Control and Vaccination Strategies 2009.. 2009.

Peiris J.S.M., Invited lecture "Confronting emerging infections: A view from Hong Kong"., Centre for Respiratory Infection, National Heart & Lung Institute, Imperial College, London, U.K.. 2009.

Peiris J.S.M., Invited lecture "Confronting emerging viral ifnections in Asia"., Life Time Achievement Symposium "Challenges in Clinical Virology in honour of Jergen Schirm. 2009.

Peiris J.S.M., Invited lecture "Emergence of the new influenza A/H1N1 2009 pandemic"., 3rd Vaccine Global Congress. Singapore. GSK Satellite Symposium "We are faced with an H1N1 influenza pandemic, now what?". 2009.

Peiris J.S.M., Invited lecture "Influenza expecting the unexpected"., SGM Spring Meeting. The global challenges of virus infection. Edinburgh, U.K.. 2010.

Peiris J.S.M., Invited lecture: Discussing the current and future challenges for influenza., World Vaccine Congress Asia 2010. Singapore. 2010.

Peiris J.S.M., Invited lecture: Epidemiology and pathogenesis of pandemic H1N1: a view from Hong Kong., Swine origin H1N1 virus: The first pandemic of the 21st Century. Atlanta, U.S.A.. 2010.

Peiris J.S.M., Invited lecture: H5N1 pathogenesis., Gordon Research Conference. Gordon Research Conference on the Biology of Acute Respiratory Infection. Ventura. U.S.A.. 2010.

Peiris J.S.M., Invited speaker: Section VIII Perspectives / Goals., Bats and emerging viral diseases workshop. Bethesda, U.S.A.. 2009.

Peiris J.S.M., Keynote speaker: From avian flu to swine flu: epidemiology and pathogenesis., First International Symposium on the infectomics of influenza A virus. University of British Columbia. Vancouver, Canada.. 2010.

Peiris J.S.M., Keynote speaker: Is there still a pandemic threat about avian influenza?, The 4th International Congress of the Asia Pacific Society of Infection Control. Macau.. 2009.

Peiris J.S.M., Lecture: Innate immunity to influenza - Friend or foe?, 2nd HKU - Pasteur Immunology Course.. 2009.

Peiris J.S.M., Plenary lecture: Influenza: Emergence and pathogenesis., 16th Symposium on Infections in the Immunocompromised Host. Hungary.. 2010.

Peiris J.S.M., Plenary talk., International Meeting on Emerging Infectious Diseases. Singapore.. 2009.

Peiris J.S.M., Scientific Organizing Committee, ICAAC, San Francisco, U.S.A.. 2009.

Peiris J.S.M., Session III: Pathogenesis - Lecture: Pre-clinical papers literature review - SARS & Influenza., XII International Symposium on Respiratory Viral Infections. Taiwan.. 2010.

Peiris J.S.M., Set up and validation of an automated PCR diagnostic and surveillance platform for influenza, Supervisor of MMedSci student Wu Yuen Ching. 2009.

Peiris J.S.M., Suppressor of cytokine singaling 3 (SOCS 3) induction in SARS coronavirus infected cells, Supervisor of MMedSci student Chow Chun Kin. 2009.

Peiris J.S.M., The D.I. Ivanovsky Institute of Virology of the Russian Academy of Medical Sciences , Medal "100 Years of Virology". 2009.

Poon L.L.M., Chan K.H., Smith G.J., Leung C.S.W., Guan Y., Yuen K.Y. and Peiris J.S.M., Molecular detection of a novel human influenza (H1N1) of pandemic potential by conventional and real-time quantitative RT-PCR assays., Clin Chem.. 2009, 55: 1555-8.

Poon L.L.M., Mak W.Y., Li O.T.W., Chan K.H., Cheung C.L., Ma S.K., Yen H., Dhanasekaran V., Guan Y. and Peiris J.S.M., Rapid Detection of Reassortment of Pandemic H1N1/2009 Influenza Virus, Clinical Chemistry. 2010, 56: 1340-4.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded Human Gammadelta T Cells Display Potent Cytotoxicities Towards Human and Avian Influenza Virus-infected Monocyte-derived Macrophages, clinical immunology. 2009, 131: s91-s92.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded gammadelta T cells display potent cytotoxicity against human and avian influenza virus-infected monocyte-derived macrophages, Journal of Infectious Diseases. 2009, 200: 858-865.

Smith G.J., Bahl J., Dhanasekaran V., Zhang J., Poon L.L.M., Chen H., Webster R.G., Peiris J.S.M. and Guan Y., Dating the emergence of pandemic influenza viruses, Proceedings of National Academic Science (USA). 2009, 106: 11709-11712.

Thach T.Q., Wong C.M., Chan K.P., Chau Y.K., Thomas G.N., Ou C., Yang L., Peiris J.S.M., Lam T.H. and Hedley A.J., Air pollutants and health outcomes: Assessment of confounding by influenza, Atmospheric Environment. 2010, 44: 1437-1442.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 Influenza A virus, Journal of Medical Virology. 2010, 82: 1-7.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Hung I.F.N., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 influenza A virus, J Med Virol. 2010, 82: 1-7.

Triana-Baltzer G.B., Babizki M., Chan M.C.W., Wong A.C.N., Aschenbrenner L.M., Campbell E.R., Li Q.X., Chan W.Y., Peiris J.S.M., Nicholls J.M. and Fang F., DAS181, a sialidase fusion protein, protects human airway epithelium against influenza virus infection: an in vitro pharmacodynamic analysis., J Antimicrob Chemother. 2010, 65: 275-84.

Tu W., Mao H., Zheng J., Liu Y., Chiu S.S.S., Qin G., Chan P.L., Lam K.T., Guan J., Zhang L., Guan Y., Yuen K.Y., Peiris J.S.M. and Lau Y.L., Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus, Journal of Virology. 2010, 84(13): 6527-6535.

Wong C.M., Yang L., Chan K.P., Ma S., He J.F., Chen P., Chan K.H. and Peiris J.S.M., Disease burden of influenza in three tropic and subtropic cities in Asia (powerpoint presentation), MISMS Oceania Regional Meeting and Workshop, 15-19 March 2010, Melbourne. Melbourne, National Institutes of Health, 2010.

Wong C.M., Yang L., Chan K.P., Chan K.H., Hedley A.J. and Peiris J.S.M., Influenza-associated hospitalisation, Hong Kong Medical Journal. 2009, 15(6) Suppl: S35-S37.

Wong C.M., Peiris J.S.M., Thach T.Q., Chau Y.K., Chan K.P., Chung R.Y.N., Thomas G.N., Lam T.H., Wong T.W. and Hedley A.J., Interaction between air pollution and respiratory viruses: Time-series studies for daily mortality and hospital admissions (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong. Hong Kong, School of Public Health/HKU, 2009, 35.

Wong C.M., Chiu S.S.S., Yang L., Wong T.W., Ma S., He J.F., Chen P., Chan K.P., Chan K.H., Wong W.H.S. and Peiris J.S.M., The burden of seasonal influenza in Hong Kong: A model-based approach with validation and comparison with other tropical/subtropical cities (poster presentation), MISMS Oceania Regional Meeting and Workshop, 15-19 March 2010, Melbourne. Melbourne, National Institutes of Health, 2010.

Wu K.M., Kwok K.O., Ning Y., Wu J.T.K., Peiris J.S.M., Cowling B.J. and Riley S., A longitudinal community study of influenza virus in Hong Kong (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong. Hong Kong, School of Public Health/HKU, 2009, 15.

Yang L., Wong C.M., Chan K.P., Chau Y.K., Ou C., Chan K.H. and Peiris J.S.M., Seasonal effects of influenza on mortality in a subtropical city, BMC Infectious Diseases. 2009, 9: 133.

Zhu H., Wang J., Wang P., Song W., Zheng Z., Chen R., Guo K., Zhang T., Peiris J.S.M., Chen H. and Guan Y., Substitution of lysine at 627 position in PB2 protein does not change virulence of the 2009 pandemic H1N1 virus in mice, Virology. 2010, 401: 1-5.

Researcher : Poon KM

List of Research Outputs

Zhou J., Huang J., Poon K.M., Chen D., Chan C.S., Ng F., Guan X.Y., Watt R.M., Lu L., Yuen K.Y. and Zheng B., Functional dissection of an IFN-alfa/belta receptor 1 promoter variant that confers higher risk to chronic hepatitis B virus infection. , J Hepat.. 2009, 51(2):: 322-332.

Researcher : Poon LLM

Project Title:	Reverse genetic for a coronavirus responsible for severe acute respiratory syndrome
Investigator(s):	Poon LLM, Guan Y
Department:	Microbiology
Source(s) of Funding:	VCO SARS Research Fund
Start Date:	07/2003

Abstract:

To generate a coronavirus-like mini vRNA GFP (green fluorescent protein) reporter system to study the transcription and replication of coronavirus; to establish a reverse genetic system of coronavirus.

Project Title:	International Conference on Options for Control of Influenza V Genetic Characterization of a Novel Coronavirus Responsible for Severe Acute Respiratory Syndrome A Coronavirus Responsible for Severe Acute Respiratory Syndrome
Investigator(s):	Poon LLM
Department:	Microbiology
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2003

Abstract:

N/A

Project Title:	Studies of mammalian, avian and chimeric influenza polymerase complexes
Investigator(s):	Poon LLM
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2007
Completion Date:	12/2009

Abstract:

To determine the transcription and replication profiling of influenza viruses with avian, mammalian, or mammalian-avian chimeric polymerase complexes in human and avian cells; to test the compatibility between avian and mammalian influenza polymerase subunits; to identify the important residues in avian PB2, PB1 and PA for host adaptation; to determine the PB2-PB1 and PB1-PA interactions in mammalian-avian chimeric complexes; to identify the host factors that might interact with viral polymerase complexes for viral transcription and replication.

Project Title:	Centre for Research into Circulating Fetal Nucleic Acids
Investigator(s):	Poon LLM
Department:	Microbiology
Source(s) of Funding:	Areas of Excellence Scheme
Start Date:	01/2008

Abstract:

Prenatal diagnosis is an indispensable component of health care. Definitive diagnostic methods in current use, e.g. amniocentesis, are invasive and pose a risk to the unborn child. In 1997, the project coordinator and his research team discovered, for the first time in the world, the presence of cell-free fetal DNA in the plasma of pregnant women, offering new possibilities for non-invasive prenatal diagnosis. The project team has further pioneered many diagnostic applications, a number of which are now used clinically by many centres globally. To maintain Hong Kong at the forefront in non-invasive prenatal diagnostic research, a Centre consisting of a multidisciplinary conglomerate of local and international researchers is formed under this Area of Excellence project, coordinated by The Chinese University of Hong Kong. The Centre will address a number of high-profile unsolved questions in the field of circulating fetal nucleic acids, including non-invasive molecular methods for the diagnosis of fetal Down syndrome. Our ultimate goal is to make safe prenatal diagnosis available to citizens around the world and to promote the development of expertise in molecular diagnostics in this region.

Project Title:	Codon biases of avian and human influenza A viruses
Investigator(s):	Poon LLM
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2009

Abstract:

(1) test the feasibility of using codon bias for virus clustering; (2) identify the codons account for the separation of human and avian viral clusters; (3) identify the condons account for the drift of codon usage in human influenza viruses; (4) determine the RNA sequences which are resistant to synonymous mutations; (5) investigate the effect of synonymous mutations in the viral lifecycle.

List of Research Outputs

Chan K.H., Lai S.T., Poon L.L.M., Guan Y., Yuen K.Y., Peiris J.S.M. and Peiris J.S.M., Analytical sensitivity of rapid influenza antigen detection tests for swine-origin influenza virus (H1N1). , J Clin Virol. . 2009, 45: 205-7.

Chan M.C.W., Chan W.Y., Yu C.L., Ho C.C., Yuen K.M., Fong J.H.M., Tang L.L.S., Lai W.W.K., Lo A.C.Y., Chui W.H., Sihoe A.D.L., Kwong D.L.W., Tsao G.S.W., Poon L.L.M., Guan Y., Nicholls J.M. and Peiris J.S.M., Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract, American Journal of Pathology. 2010, 176(4): 1828-40.

Cheung K.W., Chin W.H., Chan K.H., Schumaker M., Mak W.Y., Leung S.Y.H., Wong A., Peiris J.S.M., Petrauskene O.V. and Poon L.L.M., Evaluation of novel H1N1-specific primer-probe sets using commercial RT-PCR mixtures and a premixed reaction stored in a lyophilized format, Journal of Virological Methods. 2010, 165: 302-4.

Dhanasekaran V., Poon L.L.M., Zhu H., Ma S.K., Li O.T.W., Cheung C.L., Smith G.J., Peiris J.S.M. and Guan Y., Reassortment of pandemic H1N1/2009 influenza A virus in swine., Science. 2010, 328: 1529.

Li O.T.W. and Poon L.L.M., One step closer to universal influenza epitopes., Expert Rev Anti Infect Ther.. 2009, 7: 687-90.

Poon L.L.M., Bat guano, a gold mine for viruses, Bats and Emerging Viral Diseases Workshop, NIH, USA. 2009.

Poon L.L.M., Molecular Detection Of Influenza Viruses, Working Group Meeting On Pcr Protocols For The Detection Of Human And Avian Influenza Viruses, World Health Organization, Geneva. 2010.

Poon L.L.M., Chan K.H., Smith G.J., Leung C.S.W., Guan Y., Yuen K.Y. and Peiris J.S.M., Molecular detection of a novel human influenza (H1N1) of pandemic potential by conventional and real-time quantitative RT-PCR assays., Clin Chem.. 2009, 55: 1555-8.

Poon L.L.M., Mak W.Y., Li O.T.W., Chan K.H., Cheung C.L., Ma S.K., Yen H., Dhanasekaran V., Guan Y. and Peiris J.S.M., Rapid Detection of Reassortment of Pandemic H1N1/2009 Influenza Virus, Clinical Chemistry. 2010, 56: 1340-4.

Shih S.R., Horng J.T., Poon L.L.M., Chen T.C., Yeh J.Y., Hsieh H.P., Tseng S.N., Chiang C., Li W.L., Chao Y.S. and Hsu J.T.A., BPR2-D2 targeting viral ribonucleoprotein complex-associated function inhibits oseltamivir-resistant influenza viruses, Journal of Antimicrobial Chemotherapy. 2009, 65: 63-71.

Smith G.J., Bahl J., Dhanasekaran V., Zhang J., Poon L.L.M., Chen H., Webster R.G., Peiris J.S.M. and Guan Y., Dating the emergence of pandemic influenza viruses, Proceedings of National Academic Science (USA). 2009, 106: 11709-11712.

Yuan J., Hon C.C., Li Y., Wang D., Xu G., Zhang H., Zhou P., Poon L.L.M., Lam T.Y., Leung F.C.C. and Shi Z., Intra-species Diversity of SARS-Like Coronaviruses (CoVs) in Rhinolophus sinicus and Its Implications on the Origin of SARS-CoVs in human., Journal of general virology. 2009, 91: 1058-1062.

Yuan J., Hon C.C., Li Y., Wang D., Xu G., Zhang H., Zhou P., Poon L.L.M., Lam T.Y., Leung F.C.C. and Shi Z., Intraspecies diversity of SARS-like coronaviruses in Rhinolophus sinicus and its implications for the origin of SARS coronaviruses in humans, Journal of General Virology. 2009, 91: 1058-1062.

Researcher : Poon RWS

List of Research Outputs

Lau S.K.P., Woo P.C.Y., Wong B.H.L., Wong Y.P., Tsoi H.W., Wang M., Lee P., Xu H., Poon R.W.S., Guo R., Li K.S.M., Chan K.H., Zheng B. and Yuen K.Y., Identification and complete genome analysis of three novel paramyxoviruses, Tuhoko virus 1, 2 and 3, in fruit bats from China, Virology. 2010, 404: 106-116.

Lau S.K.P., Wong G.K.M., Poon R.W.S., Lee L.C.K., Leung K.W., Tse C.W.S., Ho P.L., Que T.L., Woo P.C.Y. and Yuen K.Y., Susceptibility Patterns Of Clinical And Fish Isolates Of Laribacter Hongkongensis: Comparison Of The Etest, Disc Diffusion And Broth Microdilution Methods, Journal Of Antimicrobial Chemotherapy. 2009, 63: 704-708.

Woo P.C.Y., Lau S.K.P., Huang Y., Lam S.F., Poon R.W.S., Tsoi H.W., Lee P., Tse H., Chan A.S., Luk G. and Yuen K.Y., Comparative analysis of six genome sequences of three novel picornaviruses, turdiviruses 1, 2 and 3, in dead wild birds and proposal of two novel genera, Orthoturdivirus and Paraturdivirus, in Picornaviridae, The Journal of general virology. 2010.

Researcher : Que TL

List of Research Outputs

Lau S.K.P., Wong G.K.M., Poon R.W.S., Lee L.C.K., Leung K.W., Tse C.W.S., Ho P.L., Que T.L., Woo P.C.Y. and Yuen K.Y., Susceptibility Patterns Of Clinical And Fish Isolates Of Laribacter Hongkongensis: Comparison Of The Etest, Disc Diffusion And Broth Microdilution Methods, Journal Of Antimicrobial Chemotherapy. 2009, 63: 704-708.

Woo P.C.Y., Lau S.K.P., Choi K.Y., Fung H.T., Shek K.C., Miao J., Chan B.Y.L., Ng K.H.L., Ngan H.Y., Ellis-Behnke R.G., Que T.L., Kam C.W. and Yuen K.Y., Resequencing microarray for detection of human adenoviruses in patients with conjunctivitis, Journal of Clinical Virology. 2010, 47: 282-285.

Researcher : Seto WH

List of Research Outputs

Cheng K.Y., Cowling B.J., Chan K.H., Fang J., Seto W.H., Yung R.W.H., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., Factors affecting QuickVue Influenza A + B rapid test performance in the community setting, Diagnostic Microbiology and Infectious Disease. 2009, 65(1): 35-41.

Cowling B.J., Chan K.H., Fang J., Cheng K.Y., Fung R.O.P., Lim Wai W.S., Sin J.W.F., Seto W.H., Yung R.W.H., Chu D.W.S., Chiu B., Lee P., Chiu M.C., Lee H.C., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., A randomized trial of face masks and hand hygiene to prevent influenza transmission in households (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong. Hong Kong, School of Public Health/HKU, 2009, 22.

Cowling B.J., Chan K.H., Fang J., Cheng K.Y., Fung R.O.P., Lim Wai W.S., Sin J.W.F., Seto W.H., Yung R.W.H., Chu D.W.S., Chiu B.C.F., Lee P.W.Y., Chiu M.C., Lee H.C., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., Facemasks and hand hygiene to prevent influenza transmission in households: a cluster randomized trial, Annals of Internal Medicine. 2009, 151(7): 437-446.

Cowling B.J., Leung G.M. and Seto W.H., Hand hygiene and virus transmission (Letter), Canadian Medical Association Journal. 2009, 181(10): 716.

Researcher : Sia SF

List of Research Outputs

Cheung P.P.H., Leung C.Y.H., Chow C.K., Ng C.F., Tsang C.L., Wu Y.O., Ma S.K., Sia S.F., Guan Y. and Peiris J.S.M., Identifying The Species-origin Of Faecal Droppings Used For Avian Influenza Virus Surveillance In Wild-birds., J Clin Virol. 2009, 46(1): 90-93.

Chua T.H., Leung C.Y.H., Fang H.E., Chow C.K., Ma S.K., Sia S.F., Ng I.H.Y., Fenwick S.G., James C.M., Chua S.B., Chew S.T., Kwang J., Peiris J.S.M. and Trevor M.E., Evaluation Of A Subunit H5 Vaccine And An Inactivated H5n2 Avian Influenza Marker Vaccine In Ducks Challenged With Vietnamese H5n1 Highly Pathogenic Avian Influenza Virus, Influenza Research And Treatment. Hindawi Publishing Corporation, 2010, 2010.

Mao H., Tu W., Qin G., Law H.K., Sia S.F., Chan P.L., Liu Y., Lam K.T., Zheng J., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, J Virol. 2009, 83(18): 9215-22.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded Human Gammadelta T Cells Display Potent Cytotoxicities Towards Human and Avian Influenza Virus-infected Monocyte-derived Macrophages, clinical immunology. 2009, 131: s91-s92.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded gammadelta T cells display potent cytotoxicity against human and avian influenza virus-infected monocyte-derived macrophages, Journal of Infectious Diseases. 2009, 200: 858-865.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Lam K.T., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses, J Infect Dis. 2009, 200(6): 858-65.

Researcher : Siu KH

List of Research Outputs

Lau W.T., Ho P.L., Kao R.Y.T., Siu K.H., Cheng V.C., Yuen K.Y. and Yam W.C., Rapid diagnosis of multidrug-resistant smear-positive pulmonary tuberculosis, International Journal of Antimicrobial agents. UK, 2010, 35(2): 202-203.

Ong D.C., Yam W.C., Siu K.H. and Lee A.S., Rapid detection of rifampicin- and isoniazid-resistant Mycobacterium tuberculosis by high-resolution melting analysis. , Journal of Clinical Microbiology. USA, 2010, 48(4): 1047-54.

Researcher : Smith GJ

Project Title:	Research into the ecology, evolution and population genetics of influenza A (H5N1) virus
Investigator(s):	Smith GJ
Department:	Microbiology
Source(s) of Funding:	National Institutes of Health, US Department of Health and Human Services - General Award
Start Date:	05/2007

Abstract:

To estimate dates of introduction and timing the movement of H5N1 virus in different countries and regions; to determine genetic factors that affect interspecies transmission and host adaptation of H5N1 influenza viruses.

Project Title:	Outstanding Young Researcher Award 2008-2009
Investigator(s):	Smith GJ
Department:	Microbiology
Source(s) of Funding:	Outstanding Young Researcher Award
Start Date:	12/2009

Abstract:

The Awards are intended to recognize, reward, and promote exceptional research accomplishments of academic and research staff.

List of Research Outputs

Chen H., Wang Y., Liu W., Zhang J., Dong B., Fan X., Jong M.D., Farrar J., Riley S., Smith G.J. and Guan Y., Serology survey of pandemic (H1N1) 2009 virus, Guangxi Province, China, Emerging Infectious Diseases. 2009, 15: 1849-50.

Dhanasekaran V., Poon L.L.M., Zhu H., Ma S.K., Li O.T.W., Cheung C.L., Smith G.J., Peiris J.S.M. and Guan Y., Reassortment of pandemic H1N1/2009 influenza A virus in swine., Science. 2010, 328: 1529.

Guan Y., Dhanasekaran V., Bahl J., Zhu H., Wang J. and Smith G.J., The emergence of pandemic influenza viruses, Protein & Cell. 2010, 1: 9-13.

Poon L.L.M., Chan K.H., Smith G.J., Leung C.S.W., Guan Y., Yuen K.Y. and Peiris J.S.M., Molecular detection of a novel human influenza (H1N1) of pandemic potential by conventional and real-time quantitative RT-PCR assays., Clin Chem.. 2009, 55: 1555-8.

Smith G.J., Bahl J., Dhanasekaran V., Zhang J., Poon L.L.M., Chen H., Webster R.G., Peiris J.S.M. and Guan Y., Dating the emergence of pandemic influenza viruses, Proceedings of National Academic Science (USA). 2009, 106: 11709-11712.

Researcher : Song W

List of Research Outputs

Liu N., Song W., Wang P., Lee K.C., Cai Z. and Chen H., Identification of unusual truncated forms of nucleocapsid protein in MDCK cells infected by Avian influenza virus (H9N2), Proteomics. 2010, 10: 1875-1879.

Zhang J., Zhang Z., Fan X., Liu Y., Wang J., Zheng Z., Chen R., Wang P., Song W., Chen H. and Guan Y., 2009 pandemic H1N1 influenza virus replicates in human lung tissues, J Infect Dis. 2010, 201: 1522-6.

Zhu H., Wang J., Wang P., Song W., Zheng Z., Chen R., Guo K., Zhang T., Peiris J.S.M., Chen H. and Guan Y., Substitution of lysine at 627 position in PB2 protein does not change virulence of the 2009 pandemic H1N1 virus in mice, Virology. 2010, 401: 1-5.

Researcher : Sui H

List of Research Outputs

Zhao G., Lin Y., Du L., Guan J., Sun S., Sui H., KOU Z., Chan C.S., Guo Y., Jiang S., Zheng B. and Zhou Y., An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses. 9. , Virol J.. 2010, 7(1):: 9.

Researcher : Tai H

List of Research Outputs

Chen H., Cheung C.L., Tai H., Zhao P., Chan J.F.W., Cheng V.C.C., Chan K.H. and Yuen K.Y., Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus, Hong Kong, China, Emerg Infect Dis.. 2009, 15: 1970-2.

Researcher : Tai JWM

List of Research Outputs

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Researcher : Tang LLS

List of Research Outputs

Chan M.C.W., Chan W.Y., Yu C.L., Ho C.C., Yuen K.M., Fong J.H.M., Tang L.L.S., Lai W.W.K., Lo A.C.Y., Chui W.H., Sihoe A.D.L., Kwong D.L.W., Tsao G.S.W., Poon L.L.M., Guan Y., Nicholls J.M. and Peiris J.S.M., Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract, American Journal of Pathology. 2010, 176(4): 1828-40.

Researcher : Tang SF

List of Research Outputs

To K.K.W., Wong S.S.Y., Cheng V.C.C., Tang S.F., Li W.S., Chan J.F.W., Seto W.K., Tse H. and Yuen K.Y., Epidemiology and clinical features of Shewanella infection over an eight-year period., Scandinavian journal of infectious diseases. 2010.

Researcher : Tang X

List of Research Outputs

Chen Z. and Tang X., The development of an AIDS mucosal vaccine., In: Tang X. and Chen Z., Viruses. 2010, 2(1): 283-297.

Researcher : Teng LL

Project Title:	Usefulness of full sequence and 5' end 527-bp 16S ribosomal RNA gene sequencing for identification of medically important aerobic Gram-positive cocci
Investigator(s):	Teng LL, Woo PCY, Lau SKP, Yuen KY
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	09/2006

Abstract:

To study usefulness of full sequence and 5' end 527-bp 16S ribosomal RNA gene sequencing for identification of medically important aerobic Gram-positive cocci.

List of Research Outputs

Lau S.K.P., Lee L.C.K., Fan Y.Y., Teng L.L., Tse C.W.S., Woo P.C.Y. and Yuen K.Y., Isolation of Laribacter hongkongensis, a novel bacterium associated with gastroenteritis, from Chinese tiger frog, International Journal of Food Microbiology. 2009, 129: 78-82.

Woo P.C.Y., Fong A.H.C., Ngan H.Y., Tam D.M.W., Teng L.L., Lau S.K.P. and Yuen K.Y., First Report Of Tsukamurella Keratitis: Association Between T. Tyrosinosolvens And T. Pulmonia And Ophthalmologic Infections, Journal Of Clinical Microbiology. 2009, 47: 1953-1956.

Woo P.C.Y., Teng L.L., Lam K.K.M., Tse C.W.S., Leung K.W., Leung A.W.S., Lau S.K.P. and Yuen K.Y., First report of Gordonibacter pamelaeae bacteremia, Journal of Clinical Microbiology . 2010, 48: 319-322.

Woo P.C.Y., Teng L.L., Wu J.K.L., Leung F.P.S., Tse H., Fung A.M.Y., Lau S.K.P. and Yuen K.Y., Guidelines for interpretation of 16S rRNA gene sequence-based results for identification of medically important aerobic Gram-positive bacteria., Journal of Medical Microbiology. 2009, 58: 1030-6.

Woo P.C.Y., Wong S.S.Y., Teng L.L., Leung K.W., Ngan H.Y., Zhao D., Tse H., Lau S.K.P. and Yuen K.Y., Leptotrichia hongkongensis sp. nov., a novel Leptotrichia species with the oral cavity as its natural reservoir, Journal of Zhejiang University-SCIENCE B. 2010, 11: 391-401.

Researcher : To KKW

Project Title:	Safety and efficacy of dose sparing intradermal S-OIV H1N1 influenza vaccination with the novel microneedle delivery device
Investigator(s):	To KKW, Hung IFN, Ho PL, Chan KH, Chan CK, Yuen KY
Department:	Microbiology
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	12/2009

Abstract:

In view of the global S-OIV H1N1 pandemics, there would be a world-wide shortage of supply for the S-OIV vaccines. In order to meet this demand, the best solution is to adopt the dose sparing intradermal vaccination, which has been shown to induce good immune responses even with low vaccine doses. We would evaluate the safety and immunogenicity of low-dose intradermal (ID) S-OIV H1N1 vaccines delivered via a novel microneedle device (Micronjet).

Project Title:	IgG2 deficiency in patients infected with 2009 H1N1 influenza virus
Investigator(s):	To KKW, Yuen KY
Department:	Microbiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2010

Abstract:

The 2009 pandemic influenza has caused more than 15000 deaths worldwide. In contrast with seasonal influenza, the current pandemic virus, 2009 H1N1 virus, has led to greater morbidity and mortality, especially in young adults, obese patients, and pregnant women. Many studies have tried to look for potential virulence determinants: virulence factors of the 1918 pandemic H1N1 virus and highly pathogenic avian H5N1 virus, involving PB2, PB-F2, NS1 and HA cleavage sequence, have not been found in the current H1N1 virus; other potential virulence determinants, including substitutions at the hemagglutinin, are under investigations. However, despite the higher virulence of the virus, most patients have mild or even asymptomatic infections. Therefore, it is highly likely that host factors play an important role in the response to 2009 H1N1 virus infection. Using genome wide expression profiling, siRNA interference studies or knockdown mutants, many host factors have been implicated to affect viral replications. In addition, different strains have inbred mice exhibited variable susceptibility to influenza virus infection. These studies have provided ample evidence of the roles of host factors in the determination of influenza virus infection. Recently, an Australian study has found an association between immunoglobulin G2 (IgG2) deficiency and severe 2009 H1N1 infection. In that study, 19 patients with severe H1N1 infection, as defined by admission to intensive care unit (ICU) for respiratory and/or vasopressor support, had significantly lower levels of IgG2 than patients with disease of moderate severity. Despite the small number of patients, this is the first study to address IgG levels and influenza disease severity. In our proposed project, we aim to look for the association between IgG2 deficiency and severe disease in Hong Kong. It is important to verify this finding because firstly, the previous study has a small samples size, and secondly, host determinants in Western countries may be different in Asian population due to underlying genetic differences.

List of Research Outputs

Chen H., Wen X., To K.K.W., Wang P., Tse H., Chan J.F.W., Tsoi H.W., Fung K.S.C., Tse C.W.S., Lee R.A., Chan K.H. and Yuen K.Y., Quasispecies of the D225G Substitution in the Hemagglutinin of Pandemic Influenza A(H1N1) 2009 Virus from Patients with Severe Disease in Hong Kong, China, J. Infectious Diseases. 2010, 201: 1517-21.

Cheng V.C., Yam W.C., Chan J.F., To K.K.W., Ho P.L. and Yuen K.Y., Clostridium difficile ribotype 027 arrives in Hong Kong, International Journal of Antimicrobial agents. UK, 2009, 34(5): 492-493.

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Cheng V.C.C., Tai J.W.M., Wong L.M.W., Chan J.F.W., Li W.S., To K.K.W., Hung I.F.N., Chan K.H., Ho P.L. and Yuen K.Y., Prevention of nosocomial transmission of swine-origin pandemic influenza virus A/H1N1 by infection control bundle. , J Hosp Infect 2010. 2010, 74: 271-7.

Li W.S., Chan K.H., To K.K.W., Wong S.S.Y., Ho P.L., Lau S.K.P., Woo P.C.Y., Tsoi H.W., Chan J.F.W., Cheng V.C.C., Zheng B., Chen H. and Yuen K.Y., Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses, Journal of Clinical Virology. 2009, 46: 325-330.

Li W.S., Hung I.F.N., To K.K.W., Chan K.H., Wong S.S.Y., Chan J.F.W., Cheng V.C.C., Tsang O.T., Lai S.T., Lau Y.L. and Yuen K.Y., The natural viral load profile of patients with pandemic swine-origin influenza A H1N1 2009 (pH1N1) and the effect of oseltamivir treatment., Chest. 2010, 137: 759-768.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Lau C.Y., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection, Clin Infect Dis.. 2010, 50: 850-859.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection, Clinical Infectious Disease. 2010, 50: 850-9.

To K.K.W., Wong S.S.Y., Cheng V.C.C., Tang S.F., Li W.S., Chan J.F.W., Seto W.K., Tse H. and Yuen K.Y., Epidemiology and clinical features of Shewanella infection over an eight-year period., Scandinavian journal of infectious diseases. 2010.

To K.K.W., Pathogenesis and Immunology of infections by Pandemic (H1N1) 2009 Influenza, World Health Organization. 2009.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 Influenza A virus, Journal of Medical Virology. 2010, 82: 1-7.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Hung I.F.N., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 influenza A virus, J Med Virol. 2010, 82: 1-7.

Woo P.C.Y., Lau S.K.P., Ngan H.Y., Tung T.K., Leung S.Y., To K.K.W., Cheng V.C.C. and Yuen K.Y., Lichtheimia hongkongensis sp. nov., a novel Lichtheimia spp. associated with rhinocerebral, gastrointestinal and cutaneous mucormycosis, Diagnostic Microbiology and Infectious Disease. 2010, 66: 274-284.

Woo P.C.Y., Leung S.Y., To K.K.W., Chan J.F.W., Ngan H.Y., Cheng V.C.C., Lau S.K.P. and Yuen K.Y., Internal transcribed spacer region sequence heterogeneity in Rhizopus microsporus: implications on molecular diagnosis in clinical microbiology laboratories, Journal of Clinical Microbiology. 2010, 48: 208-214.

Researcher : Tsang CL

List of Research Outputs

Cheung P.P.H., Leung C.Y.H., Chow C.K., Ng C.F., Tsang C.L., Wu Y.O., Ma S.K., Sia S.F., Guan Y. and Peiris J.S.M., Identifying The Species-origin Of Faecal Droppings Used For Avian Influenza Virus Surveillance In Wild-birds., J Clin Virol. 2009, 46(1): 90-93.

Researcher : Tse H

Project Title:	Isolation of Tsukamurella tyrosinosolvens from sputum specimens using a new selective medium
Investigator(s):	Tse H, Woo PCY, Lau SKP, Yuen KY
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	09/2007
Completion Date:	09/2009

Abstract:

To study the clinical significance of Tsukamurella spp. isolated from sputum specimens. Tsukamurella species are difficult to isolate in clinical specimens, and when isolated, frequently misidentified as Mycobacterium species, leading to difficulties in clinical and epidemiological studies. The proposed project will look for a simple yet more effective way of selectively isolating this bacteria and study its clinical significance.

Project Title:	Molecular characterization of anaerobic Gram-negative rods and its clinical significance
Investigator(s):	Tse H, Lau SKP, Woo PCY, Yuen KY
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	07/2008

Abstract:

(1) To provide clinicians with more accurate identification of Gram-negative anaerobic rods as a guide to the appropriate treatment regimen; (2) To clarify the clinical spectrum of diseases caused by this group of bacteria; (3) To discover novel genera and species and characterize their pathogenic role in causing human infection.

Project Title:	Multilocus sequence typing of Pseudomonas fluorescens isolates
Investigator(s):	Tse H, Yuen KY, Wong SSY
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	01/2009

Abstract:

Pseudomonas fluorescens is an environmental bacterium commonly found in a wide range of habitats, including soil, water sources, plant and animal surfaces. Because of its adaptations to grow at low temperatures, it can be found even in inhospitable environments like Antarctica and the freezer compartments of refrigerators. One resultant property of its psychrotolerance is its propensity to contaminate refrigerated products, such as food and medical products. Although usually regarded as a nonpathogenic saprophyte, P. fluorescens remains an important cause of bloodstream infections, particularly associated with the use of contaminated medical products. In fact, it is among the leading causes of blood transfusion-related infection incidents worldwide, due to its ability to grow within contaminated donor blood during storage at 4 degress celsius. Such incidents are usually associated with a very high mortality rate, as the donor blood can contain in excess of 10^8 cfu/ml of bacteria after weeks of storage and the recipient will invariably suffer from severe sepsis upon infusion of such enormous quantities of bacteria. Even the early institution of antibiotics afterwards had not been demonstrated to result in an appreciable improvement of patient survival. In the investigation of any outbreaks, contamination or medical incidents, the establishment of an epidemiological linkage is essential to delineate the sequence of events and identify any systemic problems, as well as for documentation of evidence (e.g. for medico-legal use). Such investigations will typically involve the identification of collected bacterial specimens to the strain (or finer) level. In such situations, pulsed field gel electrophoresis (PFGE) is generally considered the typing method of choice, as it is a general technique can be applied to a wide range of microorganisms. However, PFGE is time-consuming and labour-intensive, and may only be done in reference laboratories with the relevant equipment and expertise. Moreover, the results of the technique is not portable and therefore inter-lab comparisons cannot be made. The disadvantages of PFGE has spurred the development of alternative bacterial typing methods. One such alternative is multi-locus sequence typing (MLST), which involves the amplification and sequencing of multiple selected gene loci. It overcomes many of the disadvantages associated with PFGE and has the additional benefit of showing the evolutionary relationships between closely related isolates. In this proposal, we describe the modification and validation of a related MLST scheme for use in P. fluorescens. We will also apply the proposed scheme in the investigation of a previously occurred local transfusion-related incident and compare its performance to that of PFGE.

List of Research Outputs

Chan C.M., Lau S.K.P., Woo P.C.Y., Tse H., Zheng B., Chen L., Huang J. and Yuen K.Y., Identification Of Major Histocompatibility Complex Class I C Molecule As An Attachment Factor That Facilitates Coronavirus Hku1 Spike-mediated Infection, Journal of Virology. 2009, 83: 1026-1035.

Chan G.S.W., Tsoi H.W., Wong S.S.Y., Li C.L., Tse H., Un I K., Yuen K.Y. and Chan K.W., BK virus nephropathy due to KOM-3 strain, Am J Kidney Dis. 2009, 54(1): 122-6.

Chen H., Wen X., To K.K.W., Wang P., Tse H., Chan J.F.W., Tsoi H.W., Fung K.S.C., Tse C.W.S., Lee R.A., Chan K.H. and Yuen K.Y., Quasispecies of the D225G Substitution in the Hemagglutinin of Pandemic Influenza A(H1N1) 2009 Virus from Patients with Severe Disease in Hong Kong, China, J. Infectious Diseases. 2010, 201: 1517-21.

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Lau S.K.P., Li K.S.M., Huang Y., Shek C.T., Tse H., Wang M., Choi K.Y., Xu H., Lam S.F., Guo R., Chan K.H., Zheng B., Woo P.C.Y. and Yuen K.Y., Ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndrome-related Rhinolophus bat coronavirus in China reveal bats as a reservoir for acute, self-limiting infection that allows recombination events, Journal of Virology . 2010, 84: 2808-2819.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Lau C.Y., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection, Clin Infect Dis.. 2010, 50: 850-859.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection, Clinical Infectious Disease. 2010, 50: 850-9.

To K.K.W., Wong S.S.Y., Cheng V.C.C., Tang S.F., Li W.S., Chan J.F.W., Seto W.K., Tse H. and Yuen K.Y., Epidemiology and clinical features of Shewanella infection over an eight-year period., Scandinavian journal of infectious diseases. 2010.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 Influenza A virus, Journal of Medical Virology. 2010, 82: 1-7.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Hung I.F.N., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 influenza A virus, J Med Virol. 2010, 82: 1-7.

Tse H., Tsoi H.W., Leung A.S.P., Lau S.K.P., Woo P.C.Y. and Yuen K.Y., Complete genome sequence of Staphylococcus lugdunensis strain HKU09-01, Journal of Bacteriology. 2010, 192: 1471-1472.

Woo P.C.Y., Lau S.K.P., Huang Y., Lam S.F., Poon R.W.S., Tsoi H.W., Lee P., Tse H., Chan A.S., Luk G. and Yuen K.Y., Comparative analysis of six genome sequences of three novel picornaviruses, turdiviruses 1, 2 and 3, in dead wild birds and proposal of two novel genera, Orthoturdivirus and Paraturdivirus, in Picornaviridae, The Journal of general virology. 2010.

Woo P.C.Y., Teng L.L., Wu J.K.L., Leung F.P.S., Tse H., Fung A.M.Y., Lau S.K.P. and Yuen K.Y., Guidelines for interpretation of 16S rRNA gene sequence-based results for identification of medically important aerobic Gram-positive bacteria., Journal of Medical Microbiology. 2009, 58: 1030-6.

Woo P.C.Y., Wong S.S.Y., Teng L.L., Leung K.W., Ngan H.Y., Zhao D., Tse H., Lau S.K.P. and Yuen K.Y., Leptotrichia hongkongensis sp. nov., a novel Leptotrichia species with the oral cavity as its natural reservoir, Journal of Zhejiang University-SCIENCE B. 2010, 11: 391-401.

Researcher : Tsoi HW

List of Research Outputs

Chan G.S.W., Tsoi H.W., Wong S.S.Y., Li C.L., Tse H., Un I K., Yuen K.Y. and Chan K.W., BK virus nephropathy due to KOM-3 strain, Am J Kidney Dis. 2009, 54(1): 122-6.

Chen H., Wen X., To K.K.W., Wang P., Tse H., Chan J.F.W., Tsoi H.W., Fung K.S.C., Tse C.W.S., Lee R.A., Chan K.H. and Yuen K.Y., Quasispecies of the D225G Substitution in the Hemagglutinin of Pandemic Influenza A(H1N1) 2009 Virus from Patients with Severe Disease in Hong Kong, China, J. Infectious Diseases. 2010, 201: 1517-21.

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Lau S.K.P., Woo P.C.Y., Wong B.H.L., Wong Y.P., Tsoi H.W., Wang M., Lee P., Xu H., Poon R.W.S., Guo R., Li K.S.M., Chan K.H., Zheng B. and Yuen K.Y., Identification and complete genome analysis of three novel paramyxoviruses, Tuhoko virus 1, 2 and 3, in fruit bats from China, Virology. 2010, 404: 106-116.

Li W.S., Chan K.H., To K.K.W., Wong S.S.Y., Ho P.L., Lau S.K.P., Woo P.C.Y., Tsoi H.W., Chan J.F.W., Cheng V.C.C., Zheng B., Chen H. and Yuen K.Y., Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses, Journal of Clinical Virology. 2009, 46: 325-330.

Tse H., Tsoi H.W., Leung A.S.P., Lau S.K.P., Woo P.C.Y. and Yuen K.Y., Complete genome sequence of Staphylococcus lugdunensis strain HKU09-01, Journal of Bacteriology. 2010, 192: 1471-1472.

Woo P.C.Y., Lau S.K.P., Huang Y., Lam S.F., Poon R.W.S., Tsoi H.W., Lee P., Tse H., Chan A.S., Luk G. and Yuen K.Y., Comparative analysis of six genome sequences of three novel picornaviruses, turdiviruses 1, 2 and 3, in dead wild birds and proposal of two novel genera, Orthoturdivirus and Paraturdivirus, in Picornaviridae, The Journal of general virology. 2010.

Yip C.Y., Lau S.K.P., Zhou B., Zhang M.X., Tsoi H.W., Chan K.H., Chen X.C., Woo P.C.Y. and Yuen K.Y., Emergence of enterovirus 71 "double-recombinant" strains belonging to a novel genotype D originating from southern China: first evidence for combination of intratypic and intertypic recombination events in EV71., Archives of Virology. 2010.

Researcher : Tung TK

List of Research Outputs

Woo P.C.Y., Lau S.K.P., Ngan H.Y., Tung T.K., Leung S.Y., To K.K.W., Cheng V.C.C. and Yuen K.Y., Lichtheimia hongkongensis sp. nov., a novel Lichtheimia spp. associated with rhinocerebral, gastrointestinal and cutaneous mucormycosis, Diagnostic Microbiology and Infectious Disease. 2010, 66: 274-284.

Woo P.C.Y., Tung T.K., Chan K.H., Lau C.Y., Lau S.K.P. and Yuen K.Y., Cytokine profiles induced by the novel swine-origin influenza A/H1N1 virus: implications for treatment strategies, Journal of Infectious Diseases. 2010, 201: 346-353.

Researcher : Wang J

List of Research Outputs

Guan Y., Dhanasekaran V., Bahl J., Zhu H., Wang J. and Smith G.J., The emergence of pandemic influenza viruses, Protein & Cell. 2010, 1: 9-13.

Zhang J., Zhang Z., Fan X., Liu Y., Wang J., Zheng Z., Chen R., Wang P., Song W., Chen H. and Guan Y., 2009 pandemic H1N1 influenza virus replicates in human lung tissues, J Infect Dis. 2010, 201: 1522-6.

Zhu H., Wang J., Wang P., Song W., Zheng Z., Chen R., Guo K., Zhang T., Peiris J.S.M., Chen H. and Guan Y., Substitution of lysine at 627 position in PB2 protein does not change virulence of the 2009 pandemic H1N1 virus in mice, Virology. 2010, 401: 1-5.

Researcher : Wang J

List of Research Outputs

Guan Y., Dhanasekaran V., Bahl J., Zhu H., Wang J. and Smith G.J., The emergence of pandemic influenza viruses, Protein & Cell. 2010, 1: 9-13.

Researcher : Wang P

List of Research Outputs

Chen H., Wen X., To K.K.W., Wang P., Tse H., Chan J.F.W., Tsoi H.W., Fung K.S.C., Tse C.W.S., Lee R.A., Chan K.H. and Yuen K.Y., Quasispecies of the D225G Substitution in the Hemagglutinin of Pandemic Influenza A(H1N1) 2009 Virus from Patients with Severe Disease in Hong Kong, China, J. Infectious Diseases. 2010, 201: 1517-21.

Kao P.Y.P., Yang D., Lau L.S., Tsui H.W., Hu L., Dai J., Chan M.P., Chan C.M., Wang P., Zheng B., Sun J., Huang J., Madar J., Chen G., Chen H., Guan Y. and Yuen K.Y., Identification of Influenza a Nucleoprotein as an Antiviral Target, Nature Biotechnology. 2010, 28: 600-608.

Liu N., Song W., Wang P., Lee K.C., Cai Z. and Chen H., Identification of unusual truncated forms of nucleocapsid protein in MDCK cells infected by Avian influenza virus (H9N2), Proteomics. 2010, 10: 1875-1879.

Zhang J., Zhang Z., Fan X., Liu Y., Wang J., Zheng Z., Chen R., Wang P., Song W., Chen H. and Guan Y., 2009 pandemic H1N1 influenza virus replicates in human lung tissues, J Infect Dis. 2010, 201: 1522-6.

Zhu H., Wang J., Wang P., Song W., Zheng Z., Chen R., Guo K., Zhang T., Peiris J.S.M., Chen H. and Guan Y., Substitution of lysine at 627 position in PB2 protein does not change virulence of the 2009 pandemic H1N1 virus in mice, Virology. 2010, 401: 1-5.

Researcher : Wen X

List of Research Outputs

Chen H., Wen X., To K.K.W., Wang P., Tse H., Chan J.F.W., Tsoi H.W., Fung K.S.C., Tse C.W.S., Lee R.A., Chan K.H. and Yuen K.Y., Quasispecies of the D225G Substitution in the Hemagglutinin of Pandemic Influenza A(H1N1) 2009 Virus from Patients with Severe Disease in Hong Kong, China, J. Infectious Diseases. 2010, 201: 1517-21.

Researcher : Wong BHL

List of Research Outputs

Lau S.K.P., Woo P.C.Y., Wong B.H.L., Wong Y.P., Tsoi H.W., Wang M., Lee P., Xu H., Poon R.W.S., Guo R., Li K.S.M., Chan K.H., Zheng B. and Yuen K.Y., Identification and complete genome analysis of three novel paramyxoviruses, Tuhoko virus 1, 2 and 3, in fruit bats from China, Virology. 2010, 404: 106-116.

Researcher : Wong CHK

List of Research Outputs

Mok K.P., Wong C.H.K., Cheung C.Y., Chan M.C.W., Lee M.Y., Nicholls J.M., Guan Y. and Peiris J.S.M., Viral Genetic Determinants of H5N1 Influenza Viruses That Contribute to Cytokine Dysregulation, Journal of Infectious Diseases. 2009, 200(7): 1104-12.

Researcher : Wong GKM

List of Research Outputs

Lau S.K.P., Wong G.K.M., Poon R.W.S., Lee L.C.K., Leung K.W., Tse C.W.S., Ho P.L., Que T.L., Woo P.C.Y. and Yuen K.Y., Susceptibility Patterns Of Clinical And Fish Isolates Of Laribacter Hongkongensis: Comparison Of The Etest, Disc Diffusion And Broth Microdilution Methods, Journal Of Antimicrobial Chemotherapy. 2009, 63: 704-708.

Researcher : Wong LP

List of Research Outputs

Kwong A., Ng E.K.O., Leung C.P.H., Tsang W.P., Wong L.P., Kwok T.T. and Ma E.S.K., Role of miR-143 regulating DNA methyltransferases 3A in breast cancer, Ejc Supplements. 2010, 8(3): 172-173.

Ng E.K.O., Leung C.P.H., Au S., Chan A., Wong L.P., Ma E.S.K., Pang R.W.C., Chua D.T.T., Chu K.M., Law W.L., Poon R.T.P. and Kwong A., Plasma microRNA as a potential marker for breast cancer detection, The 101st Annual Meeting of the American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010.

Ng E.K.O., Kwong A., Tsang W.P., Leung C.P.H., Wong L.P., Kwok T.T. and Ma E.S.K., Role of miR-143 regulating DNA methyltransferases 3A in breast cancer, Cancer Research. 2009, 69(24): 695S-695S.

Researcher : Wong SSY

Project Title:	Molecular characterization of streptococcus bovis bacteraemia
Investigator(s):	Wong SSY, Yuen KY, Woo PCY
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To characterize 48 S. bovis strains isolated from the blood cultures of 37 bacteraemic patients over a six-year period using a combination of phenotypic and genotypic techniques. The epidemiology, underlying diseases, clinical disease associations, and outcome of S. bovis bacteraemia in relation to the different biotypes and genotypes of S. bovis will be investigated, and the molecular epidemiology of erythromycin resistance in the S. bovis strains will also be analyzed.

Project Title:	Characterization of bacterial isolates with ambiguous biochemical profiles recovered from patients with clinically significant bacteremia by 16S rRNA gene sequencing, the state-of-the-art molecular technique for bacterial identification
Investigator(s):	Wong SSY, Woo PCY, Lau SKP
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To use the state-of-the-art molecular technique for bacterial identification, 16S rRNA gene sequencing, to characterize these bacterial isolates. Novel bacterial species discovered will be further characterized.

List of Research Outputs

Chan G.S.W., Tsoi H.W., Wong S.S.Y., Li C.L., Tse H., Un I K., Yuen K.Y. and Chan K.W., BK virus nephropathy due to KOM-3 strain, Am J Kidney Dis. 2009, 54(1): 122-6.

Cheng V.C.C. and Wong S.S.Y., Infectious disease emergencies, Hong Kong Medical Diary. Hong Kong, The Federation of Medical Societies of Hong Kong, 2009, 14: 12-13.

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Li W.S., Chan K.H., To K.K.W., Wong S.S.Y., Ho P.L., Lau S.K.P., Woo P.C.Y., Tsoi H.W., Chan J.F.W., Cheng V.C.C., Zheng B., Chen H. and Yuen K.Y., Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses, Journal of Clinical Virology. 2009, 46: 325-330.

Li W.S., Hung I.F.N., To K.K.W., Chan K.H., Wong S.S.Y., Chan J.F.W., Cheng V.C.C., Tsang O.T., Lai S.T., Lau Y.L. and Yuen K.Y., The natural viral load profile of patients with pandemic swine-origin influenza A H1N1 2009 (pH1N1) and the effect of oseltamivir treatment., Chest. 2010, 137: 759-768.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Lau C.Y., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection, Clin Infect Dis.. 2010, 50: 850-859.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection, Clinical Infectious Disease. 2010, 50: 850-9.

To K.K.W., Wong S.S.Y., Cheng V.C.C., Tang S.F., Li W.S., Chan J.F.W., Seto W.K., Tse H. and Yuen K.Y., Epidemiology and clinical features of Shewanella infection over an eight-year period., Scandinavian journal of infectious diseases. 2010.

Woo P.C.Y., Wong S.S.Y., Teng L.L., Leung K.W., Ngan H.Y., Zhao D., Tse H., Lau S.K.P. and Yuen K.Y., Leptotrichia hongkongensis sp. nov., a novel Leptotrichia species with the oral cavity as its natural reservoir, Journal of Zhejiang University-SCIENCE B. 2010, 11: 391-401.

Researcher : Wong YP

List of Research Outputs

Lau S.K.P., Woo P.C.Y., Wong B.H.L., Wong Y.P., Tsoi H.W., Wang M., Lee P., Xu H., Poon R.W.S., Guo R., Li K.S.M., Chan K.H., Zheng B. and Yuen K.Y., Identification and complete genome analysis of three novel paramyxoviruses, Tuhoko virus 1, 2 and 3, in fruit bats from China, Virology. 2010, 404: 106-116.

Researcher : Woo PCY

Project Title:	Mechanistic characterization of a novel virulence factor, Mp1p, in Penicillium marneffei
Investigator(s):	Woo PCY, Chong TK, Lau SKP, Yuen KY
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	08/2007

Abstract:

To compare the organization of the context of the genes encoding the Mp1p homologues in the P. marneffei genome; to study the expression of Mp1p homologues in yeast and mold phases of P. marneffei; to study the relative importance in contribution to virulence of the 13 Mp1p homologues in P. marneffei; to characterize the mechanism of virulence of Mp1p in P. marneffei.

Project Title:	Complete genome sequencing of a newly identified rhinovirus species associated with acute respiratory illness in children
Investigator(s):	Woo PCY, Lau SKP, Yuen KY
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	09/2007
Completion Date:	09/2009

Abstract:

The objective of this study is to sequence the complete genome of a newly identified rhinovirus species associated with acute respiratory illness in children

Project Title:	Resequencing microarray for detection of viruses in patients with conjunctivitis
Investigator(s):	Woo PCY, Lau SKP, Yuen KY
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	09/2009

Abstract:

The objective of this study is to test the feasibility of using resequencing microarray for detection of viruses in patients with conjunctivitis.

Project Title:	Understanding interclass jumping between mammalian and avian coronaviruses
Investigator(s):	Woo PCY, Lau SKP, Yuen KY
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2010

Abstract:

1) To perform complete genome sequencing on the novel avian and mammalian coronaviruses; 2) To annotate the genomes of the novel avian and mammalian coronaviruses; 3) To perform comparative genomics and phylogenetic studies on the novel and existing avian and mammalian coronaviruses.

List of Research Outputs

Chan C.M., Lau S.K.P., Woo P.C.Y., Tse H., Zheng B., Chen L., Huang J. and Yuen K.Y., Identification Of Major Histocompatibility Complex Class I C Molecule As An Attachment Factor That Facilitates Coronavirus Hku1 Spike-mediated Infection, Journal of Virology. 2009, 83: 1026-1035.

Chan J.F.W., Lau S.K.P., Woo P.C.Y., Fan Y.Y., Ip J.J.K., Chan C.F., Luk J.K.H. and Yuen K.Y., Lactobacillus rhamnosus hepatic abscess associated with Mirizzi syndrome: a case report and review of the literature, Diagnostic Microbiology and Infectious Disease . 2010, 66: 94-97.

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Lau S.K.P., Yip C.Y., Lin A.W., Lee R.A., So L.Y., Lau Y.L., Chan K.H., Woo P.C.Y. and Yuen K.Y., Clinical and molecular epidemiology of human rhinovirus C in children and adults in Hong Kong reveals a possible distinct human rhinovirus C subgroup, Journal of Infectious Diseases. 2009, 200(7): 1096-1103.

Lau S.K.P., Chan K.H., Yip C.Y., Ng T.K., Tsang O.T., Woo P.C.Y. and Yuen K.Y., Confirmation of the first Hong Kong case of human infection by novel swine origin influenza A (H1N1) virus diagnosed using ultrarapid, real-time reverse transcriptase PCR, Journal of Clinical Microbiology. 2009, 47: 2344-2346.

Lau S.K.P., Li K.S.M., Huang Y., Shek C.T., Tse H., Wang M., Choi K.Y., Xu H., Lam S.F., Guo R., Chan K.H., Zheng B., Woo P.C.Y. and Yuen K.Y., Ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndrome-related Rhinolophus bat coronavirus in China reveal bats as a reservoir for acute, self-limiting infection that allows recombination events, Journal of Virology . 2010, 84: 2808-2819.

Lau S.K.P., Yip C.Y., Woo P.C.Y. and Yuen K.Y., Human rhinovirus C: a newly discovered human rhinovirus species, Emerging Health Threats Journal. 2009, 3: e2.

Lau S.K.P., Woo P.C.Y., Wong B.H.L., Wong Y.P., Tsoi H.W., Wang M., Lee P., Xu H., Poon R.W.S., Guo R., Li K.S.M., Chan K.H., Zheng B. and Yuen K.Y., Identification and complete genome analysis of three novel paramyxoviruses, Tuhoko virus 1, 2 and 3, in fruit bats from China, Virology. 2010, 404: 106-116.

Lau S.K.P., Lee L.C.K., Fan Y.Y., Teng L.L., Tse C.W.S., Woo P.C.Y. and Yuen K.Y., Isolation of Laribacter hongkongensis, a novel bacterium associated with gastroenteritis, from Chinese tiger frog, International Journal of Food Microbiology. 2009, 129: 78-82.

Lau S.K.P., Wong G.K.M., Poon R.W.S., Lee L.C.K., Leung K.W., Tse C.W.S., Ho P.L., Que T.L., Woo P.C.Y. and Yuen K.Y., Susceptibility Patterns Of Clinical And Fish Isolates Of Laribacter Hongkongensis: Comparison Of The Etest, Disc Diffusion And Broth Microdilution Methods, Journal Of Antimicrobial Chemotherapy. 2009, 63: 704-708.

Li W.S., Chan K.H., To K.K.W., Wong S.S.Y., Ho P.L., Lau S.K.P., Woo P.C.Y., Tsoi H.W., Chan J.F.W., Cheng V.C.C., Zheng B., Chen H. and Yuen K.Y., Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses, Journal of Clinical Virology. 2009, 46: 325-330.

Tse H., Tsoi H.W., Leung A.S.P., Lau S.K.P., Woo P.C.Y. and Yuen K.Y., Complete genome sequence of Staphylococcus lugdunensis strain HKU09-01, Journal of Bacteriology. 2010, 192: 1471-1472.

Woo P.C.Y., Lau S.K.P., Ngan H.Y., Tung T.K., Leung S.Y., To K.K.W., Cheng V.C.C. and Yuen K.Y., Lichtheimia hongkongensis sp. nov., a novel Lichtheimia spp. associated with rhinocerebral, gastrointestinal and cutaneous mucormycosis, Diagnostic Microbiology and Infectious Disease. 2010, 66: 274-284.

Woo P.C.Y., A novel mannoprotein superfamily in Penicillium and Aspergillus, 2009 Symposium of Medical Mycology (Taipei, Taiwan). 2009.

Woo P.C.Y., Lin A.W.C., Lau S.K.P. and Yuen K.Y., Acupuncture transmitted infections, British Medical Journal. 2010, 340: 1151-1152.

Woo P.C.Y., Lau S.K.P., Lam S.F., Lai K.Y., Huang Y., Lee P., Luk G.S.M., Dyrting K.C., Chan K.H. and Yuen K.Y., Comparative Analysis Of Complete Genome Sequences Of Three Avian Coronaviruses Reveals A Novel Group 3c Coronavirus, Journal of Virology. 2009, 83: 908-917.

Woo P.C.Y., Lau S.K.P., Huang Y., Lam S.F., Poon R.W.S., Tsoi H.W., Lee P., Tse H., Chan A.S., Luk G. and Yuen K.Y., Comparative analysis of six genome sequences of three novel picornaviruses, turdiviruses 1, 2 and 3, in dead wild birds and proposal of two novel genera, Orthoturdivirus and Paraturdivirus, in Picornaviridae, The Journal of general virology. 2010.

Woo P.C.Y., Complete genome sequence and proteome of Laribacter hongkongensis, a novel bacterium associated with gastroenteritis and traveler's diarrhea, Third Ditan international Conference on Infectious Diseases (Beijing, China). 2009.

Woo P.C.Y., Tung T.K., Chan K.H., Lau C.Y., Lau S.K.P. and Yuen K.Y., Cytokine profiles induced by the novel swine-origin influenza A/H1N1 virus: implications for treatment strategies, Journal of Infectious Diseases. 2010, 201: 346-353.

Woo P.C.Y., Lau S.K.P. and Yuen K.Y., First Report Of Methicillin-resistant Staphylococcus Aureus Septic Arthritis Complicating Acupuncture: Simple Procedure Resulting In Most Devastating Outcome, Diagnostic Microbiology And Infectious Disease. 2009, 63: 92-95.

Woo P.C.Y., Fong A.H.C., Ngan H.Y., Tam D.M.W., Teng L.L., Lau S.K.P. and Yuen K.Y., First Report Of Tsukamurella Keratitis: Association Between T. Tyrosinosolvens And T. Pulmonia And Ophthalmologic Infections, Journal Of Clinical Microbiology. 2009, 47: 1953-1956.

Woo P.C.Y., Teng L.L., Lam K.K.M., Tse C.W.S., Leung K.W., Leung A.W.S., Lau S.K.P. and Yuen K.Y., First report of Gordonibacter pamelaeae bacteremia, Journal of Clinical Microbiology . 2010, 48: 319-322.

Woo P.C.Y., Teng L.L., Wu J.K.L., Leung F.P.S., Tse H., Fung A.M.Y., Lau S.K.P. and Yuen K.Y., Guidelines for interpretation of 16S rRNA gene sequence-based results for identification of medically important aerobic Gram-positive bacteria., Journal of Medical Microbiology. 2009, 58: 1030-6.

Woo P.C.Y., Immunomodulator treatment in mice infected with influenza., Mechanisms of lung injury and immunomodulator interventions in influenza workshop, Wellcome, Ventura, USA. 2010.

Woo P.C.Y., Influenza, inflammation and immunomodulation, Cross strait workshop on emerging infectious diseases, Xiamen University, Xiamen, China. 2009.

Woo P.C.Y., Leung S.Y., To K.K.W., Chan J.F.W., Ngan H.Y., Cheng V.C.C., Lau S.K.P. and Yuen K.Y., Internal transcribed spacer region sequence heterogeneity in Rhizopus microsporus: implications on molecular diagnosis in clinical microbiology laboratories, Journal of Clinical Microbiology. 2010, 48: 208-214.

Woo P.C.Y., Laribacter hongkongensis: from discovery to complete genome sequence, Seminar in Laribacter hongkongensis (Taipei, Taiwan). 2009.

Woo P.C.Y., Wong S.S.Y., Teng L.L., Leung K.W., Ngan H.Y., Zhao D., Tse H., Lau S.K.P. and Yuen K.Y., Leptotrichia hongkongensis sp. nov., a novel Leptotrichia species with the oral cavity as its natural reservoir, Journal of Zhejiang University-SCIENCE B. 2010, 11: 391-401.

Woo P.C.Y., More and more coronaviruses, Department of Microbiolgoy, National University of Singapore. 2009.

Woo P.C.Y., Lau S.K.P., Choi K.Y., Fung H.T., Shek K.C., Miao J., Chan B.Y.L., Ng K.H.L., Ngan H.Y., Ellis-Behnke R.G., Que T.L., Kam C.W. and Yuen K.Y., Resequencing microarray for detection of human adenoviruses in patients with conjunctivitis, Journal of Clinical Virology. 2010, 47: 282-285.

Woo P.C.Y., Swine influenza: then and now., Hong Kong Medical Journal. 2009, 15: 166-167.

Woo P.C.Y., Why COX inhibitors may help patients with influenza A/H5N1 virus infections, IDSA 47th Annual meeting, Philadelphia, USA. 2009.

Yip C.Y., Lau S.K.P., Zhou B., Zhang M.X., Tsoi H.W., Chan K.H., Chen X.C., Woo P.C.Y. and Yuen K.Y., Emergence of enterovirus 71 "double-recombinant" strains belonging to a novel genotype D originating from southern China: first evidence for combination of intratypic and intertypic recombination events in EV71., Archives of Virology. 2010.

Researcher : Wu H

List of Research Outputs

Zhang H., Wang Y., Wu H., Jin D., Wen Y. and Zheng B., The Y271 And I274 Amino Acids In Reverse Transcriptase Of Human Immunodeficiency Virus-1 Are Critical To Protein Stability, In: Olivier Schwartz, Plos One. 2009, 4.

Researcher : Wu WL

List of Research Outputs

Chen Y., Luo W., Wu W.L., Fang Z., Xia L., Gui X., Chen Y., Chen H., Shih J.W.K. and Xia N., Humanized Antibodies with Broad-Spectrum Neutralization to Avian Influenza Virus H5N1, Antiviral Research. 2010, 87: 81-4.

Researcher : Wu YO

List of Research Outputs

Cheung P.P.H., Leung C.Y.H., Chow C.K., Ng C.F., Tsang C.L., Wu Y.O., Ma S.K., Sia S.F., Guan Y. and Peiris J.S.M., Identifying The Species-origin Of Faecal Droppings Used For Avian Influenza Virus Surveillance In Wild-birds., J Clin Virol. 2009, 46(1): 90-93.

Researcher : Yam WC

List of Research Outputs

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Fan M.H.M., Wong K.L., Wu S., Leung W.K., Yam W.C. and Wong T.M., Preconditioning with Porphyromonas gingivalis lipopolysaccharide may confer cardioprotection and improve recovery of the electrically induced intracellular calcium transient during ischemia and reperfusion, Journal of Periodontal Research. 2010, 45: 100-108.

Parahitiyawa N.B., Scully C., Leung W.K., Yam W.C., Jin L.J. and Samaranayake L.P., Exploring the oral bacterial flora: current status and future directions, Oral Diseases. 2010, 16: 136-145.

Researcher : Yang L

List of Research Outputs

Chen D., Zeng Y., Zhou J., Yang L., Jiang S., Huang J., Lu L. and Zheng B., Association of candidate susceptible loci with chronic infection with hepatitis B virus in a Chinese population. , J Med Virol.. 2010, 82(3):: 371-378.

Yang L. and Zheng B., Establishment of a non-transgenic mouse model for chronic hepatitis B virus infection. , European Congress of Clinical Microbiology and Infectious Diseases. Vienna, Austria.. 2010.

Researcher : Yen H

Project Title:	Identification of influenza neuraminidase sialyl substrates using glycan arrays
Investigator(s):	Yen H, Peiris JSM, Nicholls JM
Department:	Microbiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2009
Completion Date:	05/2010

Abstract:

The two surface glycoproteins of influenza A and B viruses both recognize sialic acid but with counteracting functions: hemagglutinin (HA) binds to sialic acid-containing receptors and neuraminidase (NA) hydrolyzes α-ketosidic linkage between sialic acid and the adjacent oligosaccharide (27). Sialic acid (N-acetylneuraminic acid [NeuAc], N-glycolylneuramic acid [NeuGc], and deaminoneuraminic acid [KDN]) is ubiquitously expressed on the cells surface of vertebrates, and the terminal sialic acid residues are usually linked to the adjacent oligosaccharide (galactose [Gal], N-acetylgalactosamine [GalNAc], N-acetylglucosamine [GlcNAc], or another sialic acid) via an α2,3-, α2,6- , α2,8-, or α2,9- linkage(7). For influenza viruses, selection of target cells is mediated by the HA receptor binding domain (21), although the role of NA cannot be excluded (14). The HA of Influenza viruses specifically recognize NeuAc and NeuGc sialic acid species, and the linkage connecting sialic acid and the adjacent sugar is important for determining the host range of influenza A viruses, as the avian and human influenza viruses were shown to preferentially recognize sialic acid linked to adjacent Gal via α2,3- or α2,6- linkages, respectively (19,20). In addition to the terminal sialic acid linkages, glycan array screening has identified that internal linkages as well as fucosylation, sulfation, and sialylation at the inner oligosaccharide also determined HA receptor recognition (13,23,24). A balanced HA and NA function has been shown to determine virus replication efficiency (11,27). As the HA adapts in different hosts, it is expected that the NA substrate specificity may alter correspondingly. While much interest is focused on identifying glycans recognized by the HA, it is also important to evaluate the spectrum of sialyl substrates processed by NA. Although previous studies have shown that NA from human and avian influenza virus differed in processing α2,3- or α2,6- linked sialyl receptors, only limited α2,3- or α2,6- linked synthesized glycans of simple structures were included in the studies (4,10,12,15). Due to the variety of the sialyl glycans presented in vivo, a large scale screening for potential NA substrate is needed. We first hypothesize that in addition to the terminal sialic acid linkages, the internal linkages as well as modifications of the inner oligosaccharides can affect NA substrate specificity. We further hypothesize that as HA adapts in different hosts, differences in NA specificity and activity exist between adapted influenza viruses. These hypotheses are based on the following observations. First, study of seven bacterial NAs revealed that differences in sialidase activity depend on the terminal sialic acid structure, terminal sialic acid linkages, and the structure of the adjacent sugar (7). Second, study of six influenza H1N1 viruses from different host origins revealed differences in substrate specificity as well as hydrolytic activity. While all six NAs have a higher activity for α2,3- sialosaccharides, the duck virus showed 50 times higher efficiency for α2,3- than α2,6- sialosaccharides and the human virus showed comparable efficiency in hydrolyzing α2,3- and α2,6- sialosaccharide (16). Third, a balanced HA and NA activity is needed for efficient viral growth. As the H2 and H3 that originated from an avian origin gradually adapted in human host, a change in N2 NA substrate specificity has been observed (5). The molecular determinants of NA substrate specificity was further mapped in proximity of the NA active site (12). However, the ligands for HA and NA may not always match as shown by recent human H3N2 isolates (8). Based on these studies, the specific aims of this proposal are first to apply non-infectious lentivirus-like particles (VLPs) to identify NA substrates using glycan arrays followed by determination of enzyme kinetics with the identified glycans. The benefit of using VLPs is that they retain the biological functions of surface glycoproteins, and the HA and NA expression level on a VLP should resemble that of an intact virus. Further, applying the VLP system, we can study the role of HA or NA alone or evaluate their function at the same time. We aim to focus on the N1 subtype for the preliminary experiments with long term goals of extending the study to N2 subtype as well as studying the interaction between HA and NA of a given strain. SPECIFIC AIMS: 1. Focusing on the N1 subtype, we will apply VLPs to identify the sialyl substrates of human influenza viruses, A/Hong Kong/218847/06 (H1N1) and A/Vietnam/1203/04 (H5N1), as well as avian influenza viruses, A/Duck/Alberta/35/76 (H1N1) on printed covalently linked glycan arrays. 2. Determine NA enzyme kinetics with identified glycans in a 96-well setting.

Project Title:	The role of balanced hemagglutinin-neuraminidase activity on the genesis of transmissible NA inhibitor-resistant variants in seasonal and novel pandemic influenza A H1N1 viruses
Investigator(s):	Yen H, Peiris JSM
Department:	Microbiology
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	01/2010

Abstract:

To assess the transmission potential of NA inhibitor-resistant pandemic H1N1 2009 viruses.

List of Research Outputs

Peiris J.S.M., Tu W., Yen H., Peiris J.S.M. and Yen H., A novel H1N1 virus causes the first pandemic of the 21st century, Eur J Immunol. 2009, 39(11): 2946-54.

Peiris J.S.M., Tu W. and Yen H., A novel H1N1 virus causes the first pandemic of the 21^st century, European Journal of Immunology. 2009, 39: 2946-2954.

Peiris J.S.M., Hui P.Y., Yen H., Peiris J.S.M. and Yen H., Host response to influenza virus: protection versus immunopathology, In: Adolfo Garcia-Sastre and Philippe Sansonetti, Current Opinion in Immunology. 2010, 22: 475-481.

Poon L.L.M., Mak W.Y., Li O.T.W., Chan K.H., Cheung C.L., Ma S.K., Yen H., Dhanasekaran V., Guan Y. and Peiris J.S.M., Rapid Detection of Reassortment of Pandemic H1N1/2009 Influenza Virus, Clinical Chemistry. 2010, 56: 1340-4.

Researcher : Yip CH

List of Research Outputs

Zhu H., Li L., Duan L., Yip C.H. and Guan Y., Discovery of novel species of astrovirus, coronavirus and picornavirus in bats and co-infection of viruses from different families, Bats and Emerging Infectious Diseases Workshop. 2009.

Researcher : Yip CY

Project Title:	Complete genome sequence analysis of enterovirus 71 strains from southern China
Investigator(s):	Yip CY, Lau SKP, Yuen KY, Woo PCY
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	09/2009

Abstract:

The objective of this study is to characterize the genomes of EV71 and CA16 strains detected in patients with HFMD from Shenzhen. The complete genome sequences of different EV71 and CA16 strains will be subject to bioinformatics analysis for existence of additional genotypes and potential recombination events.

Project Title:	14th International Congress on Infectious Diseases (ICID) Epidemiology of human rhinovirus C (HRV-C) in Hong Kong reveals a potential HRV-C subgroup
Investigator(s):	Yip CY
Department:	Microbiology
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	03/2010
Completion Date:	03/2010

Abstract:

N/A

List of Research Outputs

Lau S.K.P., Yip C.Y., Lin A.W., Lee R.A., So L.Y., Lau Y.L., Chan K.H., Woo P.C.Y. and Yuen K.Y., Clinical and molecular epidemiology of human rhinovirus C in children and adults in Hong Kong reveals a possible distinct human rhinovirus C subgroup, Journal of Infectious Diseases. 2009, 200(7): 1096-1103.

Lau S.K.P., Chan K.H., Yip C.Y., Ng T.K., Tsang O.T., Woo P.C.Y. and Yuen K.Y., Confirmation of the first Hong Kong case of human infection by novel swine origin influenza A (H1N1) virus diagnosed using ultrarapid, real-time reverse transcriptase PCR, Journal of Clinical Microbiology. 2009, 47: 2344-2346.

Lau S.K.P., Yip C.Y., Woo P.C.Y. and Yuen K.Y., Human rhinovirus C: a newly discovered human rhinovirus species, Emerging Health Threats Journal. 2009, 3: e2.

Tong S., Singh J., Ruone S., Humphrey C., Yip C.Y., Lau S.K.P., Anderson L.J. and Kaur T., Identification of adenoviruses in fecal specimens from wild chimpanzees (Pan trogylodytes schweinfurthii) in western Tanzania, The American Journal of Tropical Medicine and Hygiene. 2010, 82: 967-970.

Yip C.Y., Lau S.K.P., Zhou B., Zhang M.X., Tsoi H.W., Chan K.H., Chen X.C., Woo P.C.Y. and Yuen K.Y., Emergence of enterovirus 71 "double-recombinant" strains belonging to a novel genotype D originating from southern China: first evidence for combination of intratypic and intertypic recombination events in EV71., Archives of Virology. 2010.

Researcher : Yu CL

List of Research Outputs

Chan M.C.W., Chan W.Y., Yu C.L., Ho C.C., Chui W.H., Lo C.K., Yuen K.M., Guan Y., Nicholls J.M. and Peiris J.S.M., Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells, Respiratory Research. 2009, 10: 102.

Chan M.C.W., Chan W.Y., Yu C.L., Ho C.C., Yuen K.M., Fong J.H.M., Tang L.L.S., Lai W.W.K., Lo A.C.Y., Chui W.H., Sihoe A.D.L., Kwong D.L.W., Tsao G.S.W., Poon L.L.M., Guan Y., Nicholls J.M. and Peiris J.S.M., Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract, American Journal of Pathology. 2010, 176(4): 1828-40.

Chan W.Y., Yuen K.M., Yu C.L., Ho C.C., Nicholls J.M., Peiris J.S.M. and Chan M.C.W., Differential Viral Replication Kinetics And Host Innate Immune Responses By Influenza A (H5N1) Virus In Human Bronchial Epithelial Cells At Different Differentiation Stages, The 28th Annual meeting of American Society for Virology. 2009.

Chan W.Y., Yu C.L., Yuen K.M., Fong J.H.M., Lo A.C.Y., Lai W.W.K., Wong D.S.H., Nicholls J.M., Peiris J.S.M. and Chan M.C.W., Infection of influenza A (H5N1) virus in human eye epithelium, an in vitro and ex vivo study , The 28th Annual Meeting of the American Society of Virology. 2009.

Chan W.Y., Yuen K.M., Yu C.L., Ho C.C., Nicholls J.M., Peiris J.S.M. and Chan M.C.W., Influenza H5n1 And H1n1 Virus Replication And Innate Immune Responses In Bronchial Epithelial Cells Are Influenced By The State Of Differentiation, PLoS One. 2010, 5 (1): e8713.

Researcher : Yuen KM

List of Research Outputs

Chan M.C.W., Chan W.Y., Yu C.L., Ho C.C., Chui W.H., Lo C.K., Yuen K.M., Guan Y., Nicholls J.M. and Peiris J.S.M., Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells, Respiratory Research. 2009, 10: 102.

Chan W.Y., Yuen K.M., Yu C.L., Ho C.C., Nicholls J.M., Peiris J.S.M. and Chan M.C.W., Differential Viral Replication Kinetics And Host Innate Immune Responses By Influenza A (H5N1) Virus In Human Bronchial Epithelial Cells At Different Differentiation Stages, The 28th Annual meeting of American Society for Virology. 2009.

Chan W.Y., Yu C.L., Yuen K.M., Fong J.H.M., Lo A.C.Y., Lai W.W.K., Wong D.S.H., Nicholls J.M., Peiris J.S.M. and Chan M.C.W., Infection of influenza A (H5N1) virus in human eye epithelium, an in vitro and ex vivo study , The 28th Annual Meeting of the American Society of Virology. 2009.

Researcher : Yuen KY

Project Title:	Establishment of core facilities for the HKU HIV/AIDS research laboratories
Investigator(s):	Yuen KY, Zheng B, Woo PCY, Yam WC, Im SWK
Department:	Microbiology
Source(s) of Funding:	Council for the AIDS Trust Fund - General Award
Start Date:	11/2001

Abstract:

To support the development of state-of-art clinical management of HIV/AIDS founded on scientific research and clinical trials; to undertake research for expanding the knowledge base on HIV molecular epidemiology in Hong Kong and the reigon; to examine the immunological mechanisms underlying HIV pathogenesis; to study AIDS associated infectious diseases; to build expertise in HIV molecular biology and immunology.

Project Title:	Bacteraemia caused by Anaerotruncus colihominis and emended description of the species
Investigator(s):	Yuen KY, Lau SKP, Woo PCY
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	09/2005

Abstract:

To characterize a strain of Anaerotruncus colihominis recovered from the blood culture of a patient in Hong Kong and provide an emended description of the species.

Project Title:	Investigation of invasive Lasiodiplodia theobromae infections in humans
Investigator(s):	Yuen KY, Tse H, Woo PCY, Lau SKP
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	09/2007

Abstract:

Lasiodiplodia theobromae, the anamorph of Botryosphaeria rhodina, a member of the subphylum Pezizomycotina of Ascomycota, is a common plant pathogen in tropical countries. Rarely, human infections by L. theobromae can occur. In such cases, diagnosis and appropriate treatment may be delayed, and severe morbidity or mortality may result if the patient is immunocompromised. Our study aims to evaluate the usefulness of 18S rRNA gene sequencing and ITS1-5.8S-ITS2 rRNA gene cluster sequencing in the identification of this fungal pathogen. In addition, we plan to study and report the clinical aspects of such infections in detail.

Project Title:	Internal Award for CAE Membership
Investigator(s):	Yuen KY
Department:	Microbiology
Source(s) of Funding:	Internal Award for Chinese Academy of Engineering Membership
Start Date:	02/2008

Abstract:

Nil

Project Title:	Molecular characterization of human coronavirus HKU1
Investigator(s):	Yuen KY, Chan CM, Huang J, Lau SKP, Tse H, Woo PCY
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	07/2008

Abstract:

(1) To identify the key host cell receptor(s) in human cells that mediates entry of human coronavirus HKU1; (2) To investigate the interactions between the identified receptor and the viral spike protein; (3) To construct a pseudotyped virus and adapt it for use as a neutralizing antibody assay; (4) To investigate the biogenesis, subcellular localization and intracellular trafficking of HCoV-HKU1 spike protein.

Project Title:	Molecular epidemiological investigation of PARV-4-related viruses in HK and southern China
Investigator(s):	Yuen KY, Tse H, Lau SKP, Woo PCY
Department:	Microbiology
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	10/2008

Abstract:

To discover the possible animal origins of PARV4 and related viruses, and characterize their phylogenetic relationships. If possible, the epidemiology of these animal viruses would be investigated and their disease association identified.

Project Title:	Infection and Immunology
Investigator(s):	Yuen KY
Department:	Microbiology
Source(s) of Funding:	Seed Funding for Strategic Research Theme
Start Date:	11/2008

Abstract:

n/a

List of Research Outputs

Chan C.M., Lau S.K.P., Woo P.C.Y., Tse H., Zheng B., Chen L., Huang J. and Yuen K.Y., Identification Of Major Histocompatibility Complex Class I C Molecule As An Attachment Factor That Facilitates Coronavirus Hku1 Spike-mediated Infection, Journal of Virology. 2009, 83: 1026-1035.

Chan G.S.W., Tsoi H.W., Wong S.S.Y., Li C.L., Tse H., Un I K., Yuen K.Y. and Chan K.W., BK virus nephropathy due to KOM-3 strain, Am J Kidney Dis. 2009, 54(1): 122-6.

Chan J.F.W., Lau S.K.P., Woo P.C.Y., Fan Y.Y., Ip J.J.K., Chan C.F., Luk J.K.H. and Yuen K.Y., Lactobacillus rhamnosus hepatic abscess associated with Mirizzi syndrome: a case report and review of the literature, Diagnostic Microbiology and Infectious Disease . 2010, 66: 94-97.

Chan K.H., Lai S.T., Poon L.L.M., Guan Y., Yuen K.Y., Peiris J.S.M. and Peiris J.S.M., Analytical sensitivity of rapid influenza antigen detection tests for swine-origin influenza virus (H1N1). , J Clin Virol. . 2009, 45: 205-7.

Chan S.S.C., Leung Y.P., Leung A.Y.M., Lam C.L.K., Hung I., Yuen K.Y., Liang R.H.S., Johnston J.M., Chan C.K., Chu D., Liu S.H. and Lam T.H., Predictors of influenza vaccination in Chinese older patients with chronic disease in Hong Kong, The First Asia-Pacific Conference on Health Promotion and Education, 18-20 July, Chiba, Japan. 2009, 186.

Chen H., Cheung C.L., Tai H., Zhao P., Chan J.F.W., Cheng V.C.C., Chan K.H. and Yuen K.Y., Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus, Hong Kong, China, Emerg Infect Dis.. 2009, 15: 1970-2.

Chen H., Wen X., To K.K.W., Wang P., Tse H., Chan J.F.W., Tsoi H.W., Fung K.S.C., Tse C.W.S., Lee R.A., Chan K.H. and Yuen K.Y., Quasispecies of the D225G Substitution in the Hemagglutinin of Pandemic Influenza A(H1N1) 2009 Virus from Patients with Severe Disease in Hong Kong, China, J. Infectious Diseases. 2010, 201: 1517-21.

Chen J.H.K., Wong K.H., Li P., Chan K.C., Lee M.P., Lam H.Y., Cheng V.C., Yuen K.Y. and Yam W.C., Molecular epidemiological study of HIV-1 CRF01_AE transmission in Hong Kong. , Journal of acquired immunodeficiency syndromes. USA, 2009, 51(5): 530-535.

Cheng V.C., Yam W.C., Chan J.F., To K.K.W., Ho P.L. and Yuen K.Y., Clostridium difficile ribotype 027 arrives in Hong Kong, International Journal of Antimicrobial agents. UK, 2009, 34(5): 492-493.

Cheng V.C.C., Chan J.F.W., Ngan H.Y., To K.K.W., Leung S.Y., Tsoi H.W., Yam W.C., Tai J.W.M., Wong S.S.Y., Tse H., Li W.S., Lau S.K.P., Woo P.C.Y., Leung A.Y.H., Lie A.K.W., Liang R.H.S., Que T.L., Ho P.L. and Yuen K.Y., Outbreak of Intestinal Infection due to Rhizopus microsporus., Journal of Clinical Microbiology. 2009, 47: 2834-43.

Cheng V.C.C., Tai J.W.M., Wong L.M.W., Chan J.F.W., Li W.S., To K.K.W., Hung I.F.N., Chan K.H., Ho P.L. and Yuen K.Y., Prevention of nosocomial transmission of swine-origin pandemic influenza virus A/H1N1 by infection control bundle. , J Hosp Infect 2010. 2010, 74: 271-7.

Kao P.Y.P., Yang D., Lau L.S., Tsui H.W., Hu L., Dai J., Chan M.P., Chan C.M., Wang P., Zheng B., Sun J., Huang J., Madar J., Chen G., Chen H., Guan Y. and Yuen K.Y., Identification of Influenza a Nucleoprotein as an Antiviral Target, Nature Biotechnology. 2010, 28: 600-608.

Lau S.K.P., Yip C.Y., Lin A.W., Lee R.A., So L.Y., Lau Y.L., Chan K.H., Woo P.C.Y. and Yuen K.Y., Clinical and molecular epidemiology of human rhinovirus C in children and adults in Hong Kong reveals a possible distinct human rhinovirus C subgroup, Journal of Infectious Diseases. 2009, 200(7): 1096-1103.

Lau S.K.P., Chan K.H., Yip C.Y., Ng T.K., Tsang O.T., Woo P.C.Y. and Yuen K.Y., Confirmation of the first Hong Kong case of human infection by novel swine origin influenza A (H1N1) virus diagnosed using ultrarapid, real-time reverse transcriptase PCR, Journal of Clinical Microbiology. 2009, 47: 2344-2346.

Lau S.K.P., Li K.S.M., Huang Y., Shek C.T., Tse H., Wang M., Choi K.Y., Xu H., Lam S.F., Guo R., Chan K.H., Zheng B., Woo P.C.Y. and Yuen K.Y., Ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndrome-related Rhinolophus bat coronavirus in China reveal bats as a reservoir for acute, self-limiting infection that allows recombination events, Journal of Virology . 2010, 84: 2808-2819.

Lau S.K.P., Yip C.Y., Woo P.C.Y. and Yuen K.Y., Human rhinovirus C: a newly discovered human rhinovirus species, Emerging Health Threats Journal. 2009, 3: e2.

Lau S.K.P., Woo P.C.Y., Wong B.H.L., Wong Y.P., Tsoi H.W., Wang M., Lee P., Xu H., Poon R.W.S., Guo R., Li K.S.M., Chan K.H., Zheng B. and Yuen K.Y., Identification and complete genome analysis of three novel paramyxoviruses, Tuhoko virus 1, 2 and 3, in fruit bats from China, Virology. 2010, 404: 106-116.

Lau S.K.P., Lee L.C.K., Fan Y.Y., Teng L.L., Tse C.W.S., Woo P.C.Y. and Yuen K.Y., Isolation of Laribacter hongkongensis, a novel bacterium associated with gastroenteritis, from Chinese tiger frog, International Journal of Food Microbiology. 2009, 129: 78-82.

Lau S.K.P., Wong G.K.M., Poon R.W.S., Lee L.C.K., Leung K.W., Tse C.W.S., Ho P.L., Que T.L., Woo P.C.Y. and Yuen K.Y., Susceptibility Patterns Of Clinical And Fish Isolates Of Laribacter Hongkongensis: Comparison Of The Etest, Disc Diffusion And Broth Microdilution Methods, Journal Of Antimicrobial Chemotherapy. 2009, 63: 704-708.

Lau W.T., Ho P.L., Kao R.Y.T., Siu K.H., Cheng V.C., Yuen K.Y. and Yam W.C., Rapid diagnosis of multidrug-resistant smear-positive pulmonary tuberculosis, International Journal of Antimicrobial agents. UK, 2010, 35(2): 202-203.

Law H.Y., Lee D.C.W., Yuen K.Y., Peiris J.S.M. and Lau A.S.Y., Cellular response to influenza virus infection: a potential role for autophagy in CXCL10 and interferon-alpha induction and implications in pathogenesis., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Leung P.H.M., Chen J.H.K., Wong K.H., Chan K.C., Lam H.Y., Cheng V.C.C., Yuen K.Y. and Yam W.C., High prevalence of primary Enfuvirtide (ENF) resistance-associated mutations in HIV-1-infected patients in Hong Kong, Journal of Clinical Virology. 2010, 47: 273-275.

Li W.S., Chan K.H., To K.K.W., Wong S.S.Y., Ho P.L., Lau S.K.P., Woo P.C.Y., Tsoi H.W., Chan J.F.W., Cheng V.C.C., Zheng B., Chen H. and Yuen K.Y., Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses, Journal of Clinical Virology. 2009, 46: 325-330.

Li W.S., Hung I.F.N., To K.K.W., Chan K.H., Wong S.S.Y., Chan J.F.W., Cheng V.C.C., Tsang O.T., Lai S.T., Lau Y.L. and Yuen K.Y., The natural viral load profile of patients with pandemic swine-origin influenza A H1N1 2009 (pH1N1) and the effect of oseltamivir treatment., Chest. 2010, 137: 759-768.

Ng M.H., Yuen K.Y. and Zheng B., Oral DNA Composition for HBV Chronic Infection. , 2009.

Poon L.L.M., Chan K.H., Smith G.J., Leung C.S.W., Guan Y., Yuen K.Y. and Peiris J.S.M., Molecular detection of a novel human influenza (H1N1) of pandemic potential by conventional and real-time quantitative RT-PCR assays., Clin Chem.. 2009, 55: 1555-8.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Lau C.Y., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection, Clin Infect Dis.. 2010, 50: 850-859.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection, Clinical Infectious Disease. 2010, 50: 850-9.

To K.K.W., Wong S.S.Y., Cheng V.C.C., Tang S.F., Li W.S., Chan J.F.W., Seto W.K., Tse H. and Yuen K.Y., Epidemiology and clinical features of Shewanella infection over an eight-year period., Scandinavian journal of infectious diseases. 2010.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 Influenza A virus, Journal of Medical Virology. 2010, 82: 1-7.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Hung I.F.N., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 influenza A virus, J Med Virol. 2010, 82: 1-7.

Tse H., Tsoi H.W., Leung A.S.P., Lau S.K.P., Woo P.C.Y. and Yuen K.Y., Complete genome sequence of Staphylococcus lugdunensis strain HKU09-01, Journal of Bacteriology. 2010, 192: 1471-1472.

Tu W., Mao H., Zheng J., Liu Y., Chiu S.S.S., Qin G., Chan P.L., Lam K.T., Guan J., Zhang L., Guan Y., Yuen K.Y., Peiris J.S.M. and Lau Y.L., Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus, Journal of Virology. 2010, 84(13): 6527-6535.

Wong H.K., Lee C.K., Hung I.F.N., Leung J.N.S., Hong J., Yuen K.Y. and Lin C.K., Practical limitations of convalescent plasma collection: a case scenario in pandemic preparation for influenza A (H1N1) infection., Transfusion . 2010, 50: 1967-71.

Woo P.C.Y., Lau S.K.P., Ngan H.Y., Tung T.K., Leung S.Y., To K.K.W., Cheng V.C.C. and Yuen K.Y., Lichtheimia hongkongensis sp. nov., a novel Lichtheimia spp. associated with rhinocerebral, gastrointestinal and cutaneous mucormycosis, Diagnostic Microbiology and Infectious Disease. 2010, 66: 274-284.

Woo P.C.Y., Lin A.W.C., Lau S.K.P. and Yuen K.Y., Acupuncture transmitted infections, British Medical Journal. 2010, 340: 1151-1152.

Woo P.C.Y., Lau S.K.P., Lam S.F., Lai K.Y., Huang Y., Lee P., Luk G.S.M., Dyrting K.C., Chan K.H. and Yuen K.Y., Comparative Analysis Of Complete Genome Sequences Of Three Avian Coronaviruses Reveals A Novel Group 3c Coronavirus, Journal of Virology. 2009, 83: 908-917.

Woo P.C.Y., Lau S.K.P., Huang Y., Lam S.F., Poon R.W.S., Tsoi H.W., Lee P., Tse H., Chan A.S., Luk G. and Yuen K.Y., Comparative analysis of six genome sequences of three novel picornaviruses, turdiviruses 1, 2 and 3, in dead wild birds and proposal of two novel genera, Orthoturdivirus and Paraturdivirus, in Picornaviridae, The Journal of general virology. 2010.

Woo P.C.Y., Tung T.K., Chan K.H., Lau C.Y., Lau S.K.P. and Yuen K.Y., Cytokine profiles induced by the novel swine-origin influenza A/H1N1 virus: implications for treatment strategies, Journal of Infectious Diseases. 2010, 201: 346-353.

Woo P.C.Y., Lau S.K.P. and Yuen K.Y., First Report Of Methicillin-resistant Staphylococcus Aureus Septic Arthritis Complicating Acupuncture: Simple Procedure Resulting In Most Devastating Outcome, Diagnostic Microbiology And Infectious Disease. 2009, 63: 92-95.

Woo P.C.Y., Fong A.H.C., Ngan H.Y., Tam D.M.W., Teng L.L., Lau S.K.P. and Yuen K.Y., First Report Of Tsukamurella Keratitis: Association Between T. Tyrosinosolvens And T. Pulmonia And Ophthalmologic Infections, Journal Of Clinical Microbiology. 2009, 47: 1953-1956.

Woo P.C.Y., Teng L.L., Lam K.K.M., Tse C.W.S., Leung K.W., Leung A.W.S., Lau S.K.P. and Yuen K.Y., First report of Gordonibacter pamelaeae bacteremia, Journal of Clinical Microbiology . 2010, 48: 319-322.

Woo P.C.Y., Teng L.L., Wu J.K.L., Leung F.P.S., Tse H., Fung A.M.Y., Lau S.K.P. and Yuen K.Y., Guidelines for interpretation of 16S rRNA gene sequence-based results for identification of medically important aerobic Gram-positive bacteria., Journal of Medical Microbiology. 2009, 58: 1030-6.

Woo P.C.Y., Leung S.Y., To K.K.W., Chan J.F.W., Ngan H.Y., Cheng V.C.C., Lau S.K.P. and Yuen K.Y., Internal transcribed spacer region sequence heterogeneity in Rhizopus microsporus: implications on molecular diagnosis in clinical microbiology laboratories, Journal of Clinical Microbiology. 2010, 48: 208-214.

Woo P.C.Y., Wong S.S.Y., Teng L.L., Leung K.W., Ngan H.Y., Zhao D., Tse H., Lau S.K.P. and Yuen K.Y., Leptotrichia hongkongensis sp. nov., a novel Leptotrichia species with the oral cavity as its natural reservoir, Journal of Zhejiang University-SCIENCE B. 2010, 11: 391-401.

Woo P.C.Y., Lau S.K.P., Choi K.Y., Fung H.T., Shek K.C., Miao J., Chan B.Y.L., Ng K.H.L., Ngan H.Y., Ellis-Behnke R.G., Que T.L., Kam C.W. and Yuen K.Y., Resequencing microarray for detection of human adenoviruses in patients with conjunctivitis, Journal of Clinical Virology. 2010, 47: 282-285.

Wu J.T.K., Lee C.K., Cowling B.J. and Yuen K.Y., Logistical feasibility and potential benefits of a population-wide passive-immunotherapy program during an influenza pandemic, Proceedings of the National Academy of Sciences of the United States of America. 2010, 107(7): 3269-3274.

Yip C.Y., Lau S.K.P., Zhou B., Zhang M.X., Tsoi H.W., Chan K.H., Chen X.C., Woo P.C.Y. and Yuen K.Y., Emergence of enterovirus 71 "double-recombinant" strains belonging to a novel genotype D originating from southern China: first evidence for combination of intratypic and intertypic recombination events in EV71., Archives of Virology. 2010.

Zhou J., Huang J., Poon K.M., Chen D., Chan C.S., Ng F., Guan X.Y., Watt R.M., Lu L., Yuen K.Y. and Zheng B., Functional dissection of an IFN-alfa/belta receptor 1 promoter variant that confers higher risk to chronic hepatitis B virus infection. , J Hepat.. 2009, 51(2):: 322-332.

Researcher : Yung RWH

List of Research Outputs

Cowling B.J., Chan K.H., Fang J., Cheng K.Y., Fung R.O.P., Lim Wai W.S., Sin J.W.F., Seto W.H., Yung R.W.H., Chu D.W.S., Chiu B., Lee P., Chiu M.C., Lee H.C., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., A randomized trial of face masks and hand hygiene to prevent influenza transmission in households (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong. Hong Kong, School of Public Health/HKU, 2009, 22.

Cowling B.J., Chan K.H., Fang J., Cheng K.Y., Fung R.O.P., Lim Wai W.S., Sin J.W.F., Seto W.H., Yung R.W.H., Chu D.W.S., Chiu B.C.F., Lee P.W.Y., Chiu M.C., Lee H.C., Uyeki T.M., Houck P.M., Peiris J.S.M. and Leung G.M., Facemasks and hand hygiene to prevent influenza transmission in households: a cluster randomized trial, Annals of Internal Medicine. 2009, 151(7): 437-446.

Researcher : Zeng Y

List of Research Outputs

Chen D., Zeng Y., Zhou J., Yang L., Jiang S., Huang J., Lu L. and Zheng B., Association of candidate susceptible loci with chronic infection with hepatitis B virus in a Chinese population. , J Med Virol.. 2010, 82(3):: 371-378.

Researcher : Zhang G

List of Research Outputs

Zhang G., Chen M. and Zheng B., Development of recombinant Adeno-associated virus vector delivering short-hairpin RNAs to inhibit the replication of influenza. , European Congress of Clinical Microbiology and Infectious Diseases. Vienna, Austria.. 2010.

Researcher : Zhang J

List of Research Outputs

Chen H., Wang Y., Liu W., Zhang J., Dong B., Fan X., Jong M.D., Farrar J., Riley S., Smith G.J. and Guan Y., Serology survey of pandemic (H1N1) 2009 virus, Guangxi Province, China, Emerging Infectious Diseases. 2009, 15: 1849-50.

Smith G.J., Bahl J., Dhanasekaran V., Zhang J., Poon L.L.M., Chen H., Webster R.G., Peiris J.S.M. and Guan Y., Dating the emergence of pandemic influenza viruses, Proceedings of National Academic Science (USA). 2009, 106: 11709-11712.

Zhang J., Zhang Z., Fan X., Liu Y., Wang J., Zheng Z., Chen R., Wang P., Song W., Chen H. and Guan Y., 2009 pandemic H1N1 influenza virus replicates in human lung tissues, J Infect Dis. 2010, 201: 1522-6.

Researcher : Zhang L

List of Research Outputs

Tu W., Mao H., Zheng J., Liu Y., Chiu S.S.S., Qin G., Chan P.L., Lam K.T., Guan J., Zhang L., Guan Y., Yuen K.Y., Peiris J.S.M. and Lau Y.L., Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus, Journal of Virology. 2010, 84(13): 6527-6535.

Researcher : Zhang M

Project Title:	20th Annual Antibody Engineering Conference Construction and Characterization of a Chimeric Monoclonal Antibody against the Insulin-like Growth Factor-I Receptor
Investigator(s):	Zhang M
Department:	Medical Faculty
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	12/2009
Completion Date:	12/2009

Abstract:

N/A

Project Title:	Identification of HIV-1 vaccine immunogens by antibody in vitro maturation
Investigator(s):	Zhang M
Department:	Medical Faculty
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	12/2009

Abstract:

Over two decades after the discovery of Human Immunodeficiency Virus type I (HIV-1) in 1981, the development of vaccine immunogens that can elicit high-titer, potent, and broadly cross-reactive HIV-1-neutralizing antibodies (bcnAbs) remains a major challenge. Such antibodies are rare in HIV-infected individuals, and usually emerge after years of chronic infection. The lag of antibody maturation behind viral mutation often leads to viral escape and eventual disease progression. There are a small percentage of HIV-1 infected individuals whose sera exhibit high titers of bcnAbs, which contribute to their long-term no disease progression. Several monoclonal bcnAbs have been isolated from such long-term nonprogressors (LTNPs), but the immunogens designed to include their conserved epitopes did not generate the same or similar bcnAbs. Further analyses of known HIV-1 bcnAbs revealed their distinguish characteristics when compared with potent nAbs against SARS and Niphendra viruses, including high sequence diversification from the corresponding germlines, autoantibody properties, suggesting that elicitation of HIV-specific bcnAbs may require a prolonged period of time or it may never occur in most individuals. Sequence analysis of antibody libraries constructed using the mRNA isolated from the bone marrow and peripheral blood mononuclear cells (PBMCs) of subtype B LTNPs whose sera exhibited high titers of bcnAbs further revealed that the antibody gene repertoires in those subtype B LTNPs are biased to certain VH families and the third heavy chain complementary determination region (HCDR3) is on average significantly longer than the average length of HCDR3 in healthy human subjects. To explore the mechanism for elicitation of HIV-1 envelope glycoprotein (Env)-specific bcnAbs in vivo, we recently synthesized the germline antibodies of three known bcnAbs b12, 2G12 and 2F5. We found that the germline antibodies of b12, 2G12 and 2F5 did not bind HIV-1 Env, suggesting that immunization with immunogens containing b12, 2G12 and 2F5 epitopes may not trigger the naive B cells bearing the corresponding germline genes for antibody maturation and B cell proliferation. Based on these observations, we hypothesize that those LTNPs may have antibody intermediates of bcnAbs due to pre-exposure to certain immunogen(s) prior to HIV-1 infection and this “pre-existing immunity” allows the immune system to rapidly and efficiently respond to HIV-1 infection and contain the virus. The purpose of this proposed study is to identify such “pre-existing immunity” and the possible immunogens that can serve as primary immunogens leading to generation of such “pre-existing immunity”. HIV-1 Envs can serve as second immunogens leading to elicitation of potent HIV-1-specific bnAbs. To prove the concept, we will use b12 and 2F5 as model antibodies for antibody in vitro maturation study which mimics antibody maturation in vivo. B12 recognizes gp120 subunit of HIV-1 Env and its epitope overlaps the CD4 binding site (CD4bs). 2F5 recognizes the membrane proximal external region (MPER) of gp41 subunit of HIV-1 Env. The rational of this study is shown in the scheme below. Although HIV-1 isolates vary in groups, subtypes, the newly transmitted HIV-1 viruses were found to be restricted to R5-tropic virus and relatively easy to be neutralized by antibodies. We suppose that the intermediate Abs of b12 and 2F5 can bind to transmitted viruses and neutralize them. We have obtained a panel of newly transmitted HIV-1 virus isolates from NIH AIDS repository and used them in pseudovirus assay to test the isolated intermediate antibodies. Therefore, this study has two specific objectives. Objective 1: identify intermediate antibodies of b12 and 2F5 that can bind HIV-1 Env and neutralize newly transmitted HIV-1 virus. Objective 2: identify the primary immunogens that can bind b12 and 2F5 germline antibodies and elicit the coresponding intermediate antibodies. Through this study, we intend to address the question why elicitation of HIV-1-specific bcnAbs does not occur in most natural infections. We also intend to seek a solution to induction of HIV-1 specific bcnAbs by two step immunization using primary immunogens and HIV-1 Env trimers as shown in the above scheme, a novel approach for development of effective HIV-1 vaccine.

Project Title:	Development of “Two-in-One (TiO)” dual specific antibodies targeting both IGF-IR and Her 2
Investigator(s):	Zhang M
Department:	Medical Faculty
Source(s) of Funding:	Seed Funding Programme for Applied Research
Start Date:	06/2010

Abstract:

Cancer and infectious diseases are the two leading global causes of human mortality. Statistics from 1975 to 2004 by National Cancer Institute, NIH indicates that lifetime risk of being diagnosed with cancer is 1 out of 2 in man and 1 out of 3 in women. Over 30% of cancer patients have died from cancer. Monoclonal antibody (mAb) and antibody-based therapy targeting abnormal pathways have been proven to be effective in cancer diagnosis and treatment. Activation of tyrosine kinase receptors from the human epidermal growth factor receptor family (EGFR, Her2, Her3, Her4) and the insulin-like growth factor receptor type I (IGF-IR) plays a key role in the initiation and progression of breast cancer. Her2 overexpression is a validated therapeutic target, as shown by the clinical efficacy of anti-Her2 mAb trastuzumab. However, only 25–30% of patients with Her2-overexpressing tumors respond to single-agent trastuzumab, and resistance develops even in responding patients. Accumulating evidence showed that cross-talk between Her2 and IGF-IR, including receptor heterodimerization and transactivation, and elevated IGF-IR signaling have been associated with trastuzumab resistance. Therefore, co-targeting IGF-IR and Her 2 could be of clinical benefit to improve anti-Her2 therapeutic efficacy. The purpose of the proposed project is to develop dual specific antibodies, in which two antigen-binding sites are integrated into one IgG molecule, in order to co-targeting IGF-IR and Her2. Such “Two-in-One” (TiO) dual specific antibodies are expected to be more effective than monotherapy targeting Her2 alone in treatment of Her2-overexpressing breast cancer patients and in prevention of generation of resistance to anti-Her2 therapy. Furthermore, “TiO” antibodies have advantages over the conventional bi-specific antibodies in antibody production and clinical application. The conventional bi-specific antibodies, e.g. knob-hole Ig, BiTE, dAB, DVD and scFv-IgG, are in non-natural antibody format and their production is usually problematic. “TiO” Abs preserve natural IgG structure with the known pharmacokinetic behavior and in vivo effector functions. We have previously reported a human/mouse chimeric antibody, m590 that specifically bound with high affinity to cell-associated IGF-IR, blocked the binding of IGF-I and IGF-II to IGF-IR and inhibited both IGF-I and IGF-II induced phosphorylation of IGF-IR in MCF-7 breast cancer cells, suggesting its great potential for diagnosis and treatment of breast cancer. To explore the potential of m590 for clinical use, we are humanizing m590 by grafting m590 CDRs to a human antibody framework. We found that an intermediate Fab construct, in which only m590 HCDR1-3 grafted human antibody, designated Fab H10, bound to MCF-7 cells as efficiently as the parent m590, suggesting that only the heavy chain of m590 contributed to the binding to IGF-IR. This hybrid antibody can serve as a template for constructing “TiO” dual specific antibodies by grafting Her2-binding determinants (CDRs) into the light chain. To develop novel anti-Her2 mAbs, we have immunized rabbits with membrane protein extracts from human epithelial ovarian cancer cell line, SKOV-3, that over expresses Her2 and IGF-IR. The immune rabbit sera bound to SKOV-3 and MCF-7 cells in FACS analysis and inhibited the growth of both cell lines, suggesting successful immunization. We are constructing an immune rabbit Fab and VH domain antibody (dAb) libraries using PBMC and bone marrow obtained from the immunized rabbits and will select Her2-specific rabbit Abs from the library by using phage display technology. Selected anti-Her2 Fab or dAb will be used to construct TiO antibodies. Therefore, the proposed project has two specific objectives: 1. Identification of anti-Her2 neutralizing antibodies from the immune rabbit Fab and VH dAb libraries. 2. Engineering humanized anti-IGF-IR Fab H10 by grafting Her2-specific antibody CDRs to the light chain framework and optimizing the framework of the dual specific antibodies for improved biological properties to target both IGF-IR and Her2.

List of Research Outputs

Kuriakose S.A., Zentner I.J., Schön A., McFadden K., Umashankara M., Rajagopal S., Contarino M., Zhang M., Cocklin S. and Chaiken I.M., The Monoclonal Antibody M18 Suppresses HIV-1 gp120 Receptor Interactions and Envelope Spike Function, Protein Structure Initiative: 2010 NIGMS Workshop: Enabling Technologies in Structure and Function. National Institute of General Medical Sciences. April 19-21, 2010, Bethesda, Maryland, USA. 2010.

Xiao X., Chen W., Feng Y., Zhu Z., Prabakaran P., Wang Y., Zhang M., Longo N.S. and Dimitrov D.S., Germline-like Predecessors Of Broadly Neutralizing Antibodies Lack Measurable Binding To Hiv-1 Envelope Glycoproteins: Implications For Evasion Of Immune Responses And Design Of Vaccine Immunogens, Biochemical and Biophysical Research Communications . ELSEVIER, 2009, 390: 404-9.

Zhang M., Broadly Cross-Reactive HIV-1-Specific Antibodies for Prevention and Treatment of HIV, U.S. Provisional Application No. 61/345,425 filed 17 May 2010. 2010.

Zhang M., Editorial board member for Journal of Bioanalysis & Biomedicine, 2009.

Zhang M., Editorial board member for Journal of Bioequivalence & Bioavailability, 2009.

Zhang M., Human Monoclonal Antibodies against Infectious Diseases and Cancer , AIDS Institute and HKU Pasteur Research Centre Joint Seminar, June 10, 2010, Hong Kong, China . Hong Kong, 2010.

Zhang M., Humanized Anti-IGF-IR Monoclonal Antibodies and Uses Thereof, U.S. Provisional Application No. 61/266,681 filed 4 December 2009. 2009.

Zhang M., Is An Effective HIV-1 Vaccine Possible?, The Second China AIDS Vaccine Forum, May 2010, Shanghai, China . Shanghai, 2010.

Zhang M., Is an Effective HIV-1 Vaccine Possible? , Research Center for Infectious Disease and Immunology, June 21, 2010, Hong Kong . 2010.

Zhang M., Nominated as a representative of young investigators in China to attend the AIDS Vaccine for Asia Network (AVAN) meeting held on June 29-30, 2010 in Thailand; Offered expert opinions for establishment of AIDS Vaccine Network in Asia, and for developing and crystallizing a strategic plan and an action plan for AVAN., 2010.

Zhang M. and Borges A.R., Potent and broad neutralizing activity of a single chain antibody fragment against cell-free and cell-associated HIV-1, In: Janice M. Reichert, Ph.D., MAbs. • 1002 West Ave., Austin, TX 78701, Landes Bioscience, 2010, 2.

Zhang M., The best oral presentation at the 2nd China AIDS Vaccine Forum held in Shanghai in May, 2010, and awarded by NIH for attending the XVIII International AIDS Conference to be held in Vienna, Austria from July 18 to 23, 2010. All the costs are covered by the NIH. , NIH, US Department of Health and Human Services. 2010.

Researcher : Zhang Q

Project Title:	Construction and Characterization of a Full-Length Infectious Molecular Clone from the HIV Type 1 CRF08_BC Isolated in China
Investigator(s):	Zhang Q, Zheng B
Department:	Microbiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2009

Abstract:

To isolate a HIV-1 circulating recombinant form CRF08_BC virus strain from an injecting drug user (IDU) of the GuangXi Province of China and to get the full-length genomic sequence of the virus. To clone the full-length genome of this virus and rescue it by the functional 5’ LTR (long terminal repeat region) and 3’ LTR from pNL4-3 to produce a chimeric infectious molecular clone as a virus model for the subsequent research about CRF_08BC. To character the replication kinetics of the recovered virus from the constructed infectious clone. To analyze the phylogenetic relationship between the viral genome of the infectious clone and standard representatives of all HIV-1 major group (M) subtypes and circulating recombinant forms.

Researcher : Zhao G

List of Research Outputs

Du L., Zhao G., Chan C.S., Li L., He Y., Zhou Y., Zheng B. and Jiang S., A 219-mer CHO-expressing RBD of SARS-CoV S protein induces potent immune responses and protective immunity. , Viral Immunol. . 2010, 23(2):: 211-219.

Du L., Zhao G., Li L., He Y., Zhou Y., Zheng B. and Jiang S., Antigenicity and immunogenicity of SARS-CoV S protein receptor-binding domain stably expressed in CHO cells., Biochem Biophys Res Commun . 2009, 384(4):: 486-90.

Du L., Zhao G., Chan C.S., Sun S., Chen M., Liu Z., Guo H., He Y., Zhou Y., Zheng B. and Jiang S., Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity. , Virology. 2009, 393:: 144-150.

Zhao G., Lin Y., Du L., Guan J., Sun S., Sui H., KOU Z., Chan C.S., Guo Y., Jiang S., Zheng B. and Zhou Y., An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses. 9. , Virol J.. 2010, 7(1):: 9.

Researcher : Zhao P

List of Research Outputs

Chen H., Cheung C.L., Tai H., Zhao P., Chan J.F.W., Cheng V.C.C., Chan K.H. and Yuen K.Y., Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus, Hong Kong, China, Emerg Infect Dis.. 2009, 15: 1970-2.

Researcher : Zheng B

Project Title:	CCR5 expression on antigen-presenting cens in HIV infection
Investigator(s):	Zheng B, Lee SS
Department:	Microbiology
Source(s) of Funding:	Council for the AIDS Trust Fund - General Award
Start Date:	01/2001

Abstract:

To describe the pattern of CCR5 expression on APC in HIV infection; to correlate this pattern to HIV infected APC; to determine the functional and/or quantitative deficiency in CCR5 expressing APC.

Project Title:	The pattern of chemokine receptor polymorphism in healthy and HIV positive Chinese adults
Investigator(s):	Zheng B, Lee SS
Department:	Microbiology
Source(s) of Funding:	Council for the AIDS Trust Fund - General Award
Start Date:	01/2001

Abstract:

To determine the prevalence of the major forms of CCR5 promoter and CCR2 polymorphism in healthy Chinese adults; to compare the pattern between healthy adults and HIV infected individuals in Hong Kong.

Project Title:	A longitudinal study of HIV-1 drug-resistance for improving management of patients on HARRT (MSS 140R)
Investigator(s):	Zheng B, Lu L, Chan KW
Department:	Microbiology
Source(s) of Funding:	Council for the AIDS Trust Fund - General Award
Start Date:	07/2006

Abstract:

To define and confirm the specificities of viral gene mutations in non-B subtypes of HIV-1 that are responsible for drug resistance, identify potential drug-resistance before treatment failure, and analyze the circumstances for the causation of latent infection by drug-resistant viruses.

Project Title:	A feasibility study on the inhibition of avian infuenza virus H5N1 replication using siRNA
Investigator(s):	Zheng B, Yuen KY, Jin D
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2007
Completion Date:	12/2009

Abstract:

(1) Rational design and evalution of additional siRNAs targeting multiple structural and non-structural genes of H5N1 virus in cultured cells; (2) analysis of the synergistic antiviral effects of different siRNAs obtained; (3) development of effective non-viral and viral based systems for delivering H5N1-targeting siRNAs in mice and evaluation of the antiviral effects of selective siRNAs in vivo.

Project Title:	Study of vaccine HA-M2 against H5N1 avian influenza virus
Investigator(s):	Zheng B
Department:	Microbiology
Source(s) of Funding:	Matching Fund for Hi-Tech Research and Development Program of China (863 Projects)
Start Date:	08/2007

Abstract:

To study vaccine HA-M2 against H5N1 avian influenza virus.

Project Title:	Study of AAV- and peptide-based vaccine candidates against influenza virus H5N1 infection in animal model
Investigator(s):	Zheng B, Yuen KY
Department:	Microbiology
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	11/2007

Abstract:

To evaluate immune responses of the rAAV vaccination boosted by the pooled peptides in mouse model; to evaluate cross-protective efficts of the vaccine candidates in H5N1 virus infected animal model.

Project Title:	A feasibility study of human T cell epitope-based vaccines against H5N1 avian influenza virus
Investigator(s):	Zheng B, Yuen KY
Department:	Microbiology
Source(s) of Funding:	France/Hong Kong Joint Research Scheme - Travel Grants
Start Date:	01/2008
Completion Date:	12/2009

Abstract:

1) identification of HLA-A2/DR1 restricted Th and CTL epitopes specific to H5N1 virus in vaccinated HLA-A2+DR1+transgenic mice; 2) evaluation of immune response in A2+DR1+mice primed by an AAV-based vaccines and boosted by pool peptides corresponding to T cell epitopes derived from different strains of the virus; 3) evaluation of cross-protective effects of AAV-based and T cell epitope-based vaccines in animal models of H5N1 infection.

Project Title:	The Role of Complement Activation in Severe Pneumonia Caused by Avian Influenza Virus H5N1 Infection
Investigator(s):	Zheng B, Jin D, Yuen KY
Department:	Microbiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2009
Completion Date:	12/2009

Abstract:

(1) To establish the role of complement activation in H5N1-associated severe pneumonia using C3-/- and C5-/- mice; (2) Protocol I. Fourteen C3-/- (KO) mice and 14 C57BL/6 mice (wild type of KO mouse), as well as 14 B10.D2/oSnJ (C5-) and 14 B10.D2/nSnJ (C5+) mice, are given intranasal inoculation of H5N1 virus. II. Five mice in each group are monitored for signs and symptoms, temperature, body weight, survival days and survival rate. III. Three mice of each group are respectively sacrificed on day 4, 6 and 8 after the inoculation (a total of 9 mice for each group). IV. Lung tissues and blood samples are collected from these mice. Sera are inactivated at 56ºC and stored at -80ºC. V. Half lung tissue from each mouse are fixed with 10% formalin solution, whereas RNA is extracted from the other half tissue and then reverse-transcribed to cDNA according to our established method [29-34]; (3) Protocol (continued) VI. These samples will be also collected from the mice inoculated with PBS (3 mice per time-point) as negative controls. VII. Pathological changes are detected by H&E staining as described previously [35-37]. VIII. Tissue depositions of C1q, C3, C4, FB and MBL-C in formalin-fixed tissues are detected by immunohistochemical assays in accordance with the established methods [32-37] and those described above in our preliminary study. IX. The replication of H5N1 virus are quantified by real-time PCR using cDNA samples derived from the tissues while antibodies to H5N1 virus will be tested by hemagglutination-inhibition assay (HIA) and ELISA, according to the established protocols [1, 2, 4, 38]. X. Soluble complement activation products, i.e. C3a & C5a, and pro-inflammatory cytokines and chemokines, such as TNF-a. IFN-a, IFN-r, IL-1, IL-6, MCP-1, KC, MIP-2 and RANTES in serum samples are tested by ELISA in accordance with an established protocol [34-40]; (4) Data analysis: I. Proteins from each of the three pathways of complement activation, i.e. C1 & C4 (classical), MBL (lectin), FB (alternative), C3a and C5a (all pathways), will be compared among samples obtained from different groups and time-points, and related to pathological changes and the progression of inflammation. II. Generations of pro-inflammatory cytokines and chemokines will be compared between samples obtained from C57BL/6 (C3+) versus C3-/- and B10.D2/nSnJ (C5+) versus B10.D2/oSnJ (C5-) mice, at different time-points, and related to pathological changes, expression levels and deposition of complement activation products; (5) Data analysis (continued): III. Signs and symptoms, temperature, body weight lost, survival days and survival rates will be compared among different groups of mice and correlated to the results of complement activation products and levels of pro-inflammatory cytokines. IV. Expression and deposition of complement activation products will also be correlated to levels of viral load and virus specific antibodies in the samples collected at different time-points, which will give us some suggestions as to whether viral protein-antibody immune complex (IC) might play a role in complement activation.

Project Title:	Cross-protective efficacy of immunization with different forms of M2 vaccines and their combinations with HA vaccines against highly pathogenic H5N1 influenza A viruses in mice
Investigator(s):	Zheng B, Yuen KY
Department:	Microbiology
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	10/2009

Abstract:

1) To evaluate protective effect of M2e-ASP, rAAV-M2 and peptide-M2e vaccinations against H5N1 viral infection in mouse model; 2) assess protective efficacy of immunications with M2e-ASP, rAAV-M2 and peptide-M2e against challenge with hormologous and heterologous strains of H5N1 virus in animal model; 3) evaluate protective efficacy of HA andrAAV-Ha vaccinations against challenge with homologous and heterologous strains of H5N1 virus in animal model; 4) evaluate cross-protective efficacy of different combinations of M2e-based and HA-based vaccine candidates against challenge with homologous and heterologous strains of H5N1 virus in animal model. The knowledge gained in this study will lay a foundation for developing effective and universal vaccines against H5N1 influenza virus infection.

Project Title:	HEP DART 2009 HBsAg-HBIg complex modulates antigen presentation of dendritic cells from chronic hepatitis B patients
Investigator(s):	Zheng B
Department:	Microbiology
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	12/2009
Completion Date:	12/2009

Abstract:

N/A

Project Title:	Co-administration of antiviral and anti-inflammatory agents against avian influenza virus H5N1 infection in animal model
Investigator(s):	Zheng B, Yuen KY, Jin D
Department:	Microbiology
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	01/2010

Abstract:

(1) To define antiviral and non-Cox-2 inhibitor anti-inflammatory effects for individual agent; (2) To evaluate effects of the cocktail treatments using non-COX-2 immunomodulators: (3) to assess the cocktail treatment using COX-2 inhibitors and non-COX-2 immunomodulators; (4) to optimize dosing, timing and administration route of the effective cocktail treatments.

List of Research Outputs

Chan C.M., Lau S.K.P., Woo P.C.Y., Tse H., Zheng B., Chen L., Huang J. and Yuen K.Y., Identification Of Major Histocompatibility Complex Class I C Molecule As An Attachment Factor That Facilitates Coronavirus Hku1 Spike-mediated Infection, Journal of Virology. 2009, 83: 1026-1035.

Chen D. and Zheng B., Association of candidate susceptible loci with chronic hepatitis B virus infection in Chinese population. ., European Congress of Clinical Microbiology and Infectious Diseases. Vienna, Austria. 2010.

Chen D., Zeng Y., Zhou J., Yang L., Jiang S., Huang J., Lu L. and Zheng B., Association of candidate susceptible loci with chronic infection with hepatitis B virus in a Chinese population. , J Med Virol.. 2010, 82(3):: 371-378.

Chen M., Huang J., Hu L., Zheng B., Chen L., Tsang S.L. and Guan X.Y., Transgenic CHD1L expression in mouse induces spontaneous tumors, PLoS One. 2009, 4: e6727.

Du L., Zhao G., Chan C.S., Li L., He Y., Zhou Y., Zheng B. and Jiang S., A 219-mer CHO-expressing RBD of SARS-CoV S protein induces potent immune responses and protective immunity. , Viral Immunol. . 2010, 23(2):: 211-219.

Du L., Zhao G., Li L., He Y., Zhou Y., Zheng B. and Jiang S., Antigenicity and immunogenicity of SARS-CoV S protein receptor-binding domain stably expressed in CHO cells., Biochem Biophys Res Commun . 2009, 384(4):: 486-90.

Du L., Zhao G., Chan C.S., Sun S., Chen M., Liu Z., Guo H., He Y., Zhou Y., Zheng B. and Jiang S., Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity. , Virology. 2009, 393:: 144-150.

Kao P.Y.P., Yang D., Lau L.S., Tsui H.W., Hu L., Dai J., Chan M.P., Chan C.M., Wang P., Zheng B., Sun J., Huang J., Madar J., Chen G., Chen H., Guan Y. and Yuen K.Y., Identification of Influenza a Nucleoprotein as an Antiviral Target, Nature Biotechnology. 2010, 28: 600-608.

Lau S.K.P., Li K.S.M., Huang Y., Shek C.T., Tse H., Wang M., Choi K.Y., Xu H., Lam S.F., Guo R., Chan K.H., Zheng B., Woo P.C.Y. and Yuen K.Y., Ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndrome-related Rhinolophus bat coronavirus in China reveal bats as a reservoir for acute, self-limiting infection that allows recombination events, Journal of Virology . 2010, 84: 2808-2819.

Lau S.K.P., Woo P.C.Y., Wong B.H.L., Wong Y.P., Tsoi H.W., Wang M., Lee P., Xu H., Poon R.W.S., Guo R., Li K.S.M., Chan K.H., Zheng B. and Yuen K.Y., Identification and complete genome analysis of three novel paramyxoviruses, Tuhoko virus 1, 2 and 3, in fruit bats from China, Virology. 2010, 404: 106-116.

Li W.S., Chan K.H., To K.K.W., Wong S.S.Y., Ho P.L., Lau S.K.P., Woo P.C.Y., Tsoi H.W., Chan J.F.W., Cheng V.C.C., Zheng B., Chen H. and Yuen K.Y., Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses, Journal of Clinical Virology. 2009, 46: 325-330.

Li Y., Zhao J.K., Wang M., Han Z.G., Cai W.P., Zheng B. and Xu H.F., Current antibody-based immunoassay algorithm failed to confirm three late-stage AIDS cases in China: case report. , Virol J.. 2010, 7(1):: 58.

Lin Y., Tanner J.A. and Zheng B., In vivo selection and characterization of DNA aptamers against H5N1 virus nucleoprotein. , European Congress of Clinical Microbiology and Infectious Diseases. Vienna, Austria. 2010.

Lin Y., Shum K.T., Tanner J.A. and Zheng B., Study of DNA aptamers binding H5N1 virus nucleoprotein. , Thailand Conference on Emerging Infectious and Neglected Diseases. Chonbrti, Thailand.. 2010.

Ma S.K.Y., Tang K.H., Chan Y.P., Lee K.W., Castilho A.G., Ng I.O.L., Man K., To K.F., Zheng B., Chan K.W. and Guan X.Y., miR-130b is preferentially upregulated in CD133+ liver cancer stem cells and regulates tumor growth and self-renewal via tumor protein 53-induced nuclear protein 1, Gordon Research Conference - Stem Cells and Cancer. 2009.

Ng M.H., Yuen K.Y. and Zheng B., Oral DNA Composition for HBV Chronic Infection. , 2009.

Siu K.L., Chan C.P., Chan C.S., Zheng B. and Jin D., Severe acute respiratory syndrome coronavirus nucleocapsid protein does not modulate transcription of human FGL2 gene., J. Gen. Virol.. 2009, 90: 2107-2113.

Tanner J.A., Zheng B., Lin Y., Kimura M., Lui E.L.H. and Shum K.T., Selection, validation and delivery of DNA aptamers against infectious disease targets. , 5th Annual Meeting of the Oligonucleotide Therapeutics Society, Fukuoka, Japan . 2009.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Lau C.Y., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection, Clin Infect Dis.. 2010, 50: 850-859.

To K.K.W., Hung I.F.N., Li W.S., Lee K.L., Koo C.K., Yan W.W., Liu R., Ho K.Y., Chu K.H., Watt C.L., Luk W.K., Lai K.Y., Chow F.L., Mok T., Buckley T., Chan J.F.W., Wong S.S.Y., Zheng B., Chen H., Tse H., Cheng V.C.C., Chan K.H. and Yuen K.Y., Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection, Clinical Infectious Disease. 2010, 50: 850-9.

Yang L. and Zheng B., Establishment of a non-transgenic mouse model for chronic hepatitis B virus infection. , European Congress of Clinical Microbiology and Infectious Diseases. Vienna, Austria.. 2010.

Yang M., Sun L., Wang S., Xu H., Zheng B., Cao X. and Lu L., Cutting Edge: Novel function of BAFF in the induction of IL-10-producing regulatory B cells, Journal of Immunology. 2010, 184: 3321-3325.

Zhang G., Chen M. and Zheng B., Development of recombinant Adeno-associated virus vector delivering short-hairpin RNAs to inhibit the replication of influenza. , European Congress of Clinical Microbiology and Infectious Diseases. Vienna, Austria.. 2010.

Zhang H., Wang Y., Wu H., Jin D., Wen Y. and Zheng B., The Y271 And I274 Amino Acids In Reverse Transcriptase Of Human Immunodeficiency Virus-1 Are Critical To Protein Stability, In: Olivier Schwartz, Plos One. 2009, 4.

Zhao G., Lin Y., Du L., Guan J., Sun S., Sui H., KOU Z., Chan C.S., Guo Y., Jiang S., Zheng B. and Zhou Y., An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses. 9. , Virol J.. 2010, 7(1):: 9.

Zheng B., Sze J., Cheung K.C., Lin M.C. and Kung H.F., Super Interferons for the Treatment of Bird Flu, Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society, & International Society for Interferon and Cytokine Research; Portugal; 17-21 October, 2009.. 2009.

Zheng B., Yao X., Zhou J. and Wen Y.M., complex modulates antigen presentation of dendritic cells from chronic hepatitis B patients. , HEP DART 2009Frontiers in Drug Development for Viral Hepatitis. The Big Island, Hawaii, USA. 2009.

Zhou J., Huang J., Poon K.M., Chen D., Chan C.S., Ng F., Guan X.Y., Watt R.M., Lu L., Yuen K.Y. and Zheng B., Functional dissection of an IFN-alfa/belta receptor 1 promoter variant that confers higher risk to chronic hepatitis B virus infection. , J Hepat.. 2009, 51(2):: 322-332.

Researcher : Zhou J

Project Title:	A feasibility study on the inhibition of respiratory syncytial virus infection using siRNAs with a unique motif
Investigator(s):	Zhou J, Zheng B
Department:	Microbiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2010

Abstract:

Respiratory syncytial virus (RSV) infection is the leading cause of acute upper and lower respiratory track infection in infant and children worldwide. In Hong Kong, it accounts for 90% of hospital admissions classified as bronchiolitis or pneumonia during peak seasons. Almost all the children are infected by 2 years of age. Most of them suffered mild symptoms such as rhinorrhea, cough, fever and sometimes wheeze, which basically resolved within 2 weeks. However, 25-40% of children present signs of low respiratory track infection, indicative of a viral bronchiolitis and pneumonia. A rough estimation of the global annual infection figure for RSV can be around 64 million and mortality could be as high as 160,000. Notably, children who contract severe RSV infections in infancy have a higher incidence of wheezing and asthma later in life. In elderly persons, RSV cause pneumonia, exacerbation of chronic pulmonary diseases and has been recognized as an important cause of morbidity from influenza-like illness in elderly. These studies serve as the basis to develop effective antiviral and vaccine against RSV infection. Although RSV was identified more than 50 years ago, treatment for the infected patients remains basically supportive. The endeavors to develop safe and effective vaccine or anti-RSV treatments ended with few successes. Certain properties of RSV F protein make it a promising target for treatment and prophylaxis since it is highly conserved and anti-F antibody induced by primary infection is cross-reactive between the two major subtypes of RSV. A humanized monoclonal antibody against F protein is the only licensed prophylactic drug for RSV currently. However its clinical effectiveness is controversial. Promising inhibitors of F protein were abandoned partly due to the resistant mutations present in F gene. Therefore, there is a major unmet need for an effective treatment for the RSV infection in pediatric and adult populations. Faced with the difficulties in traditional antiviral strategies, RNAi showed great promise as an antiviral against this virus. The small interfering RNA (siRNA, 21-23 nucleotide oligo) duplex has been proven to be a potent agent for knocking out gene expression in mammalian cells through mRNA disruption. It has also been reported that siRNA can effectively inhibit viral replication and infection both in vitro and in vivo, including HIV-1, influenza, dengue, polio, hepatitis B, and hepatitis C viruses. We have carried out studies to evaluate the inhibition of avian influenza A virus H5N1 by small interfering RNAs. We found that the siRNAs with a unique motif exhibited extradinary strong antiviral effect in virally infected experimental animals. The underlying mechansims could be attributed, at least in part, to an our latest observation that a unique motif may stimulate early production of -defensin in respiratory tract. The proposed study will extend this work towards the development of effective RNAi-based therapeutic agents against RSV infection. The feasibility of using RNAi to inhibit the replication of the RSV will be assessed in both cultured cells and animal models. The objectives of our study are to (1) identify siRNAs targeting multiple structural and non-structural RSV genes by evaluating their antiviral effects in cell cultures; (2) establish mouse model(s) with lethal RSV infection; and (3) evaluate antiviral effects of siRNAs with and without the unique motif in animal models.

List of Research Outputs

Chen D., Zeng Y., Zhou J., Yang L., Jiang S., Huang J., Lu L. and Zheng B., Association of candidate susceptible loci with chronic infection with hepatitis B virus in a Chinese population. , J Med Virol.. 2010, 82(3):: 371-378.

Zheng B., Yao X., Zhou J. and Wen Y.M., complex modulates antigen presentation of dendritic cells from chronic hepatitis B patients. , HEP DART 2009Frontiers in Drug Development for Viral Hepatitis. The Big Island, Hawaii, USA. 2009.

Zhou J., Huang J., Poon K.M., Chen D., Chan C.S., Ng F., Guan X.Y., Watt R.M., Lu L., Yuen K.Y. and Zheng B., Functional dissection of an IFN-alfa/belta receptor 1 promoter variant that confers higher risk to chronic hepatitis B virus infection. , J Hepat.. 2009, 51(2):: 322-332.

Researcher : Zhu H

List of Research Outputs

Dhanasekaran V., Poon L.L.M., Zhu H., Ma S.K., Li O.T.W., Cheung C.L., Smith G.J., Peiris J.S.M. and Guan Y., Reassortment of pandemic H1N1/2009 influenza A virus in swine., Science. 2010, 328: 1529.

Guan Y., Dhanasekaran V., Bahl J., Zhu H., Wang J. and Smith G.J., The emergence of pandemic influenza viruses, Protein & Cell. 2010, 1: 9-13.

Zhu H., Li L., Duan L., Yip C.H. and Guan Y., Discovery of novel species of astrovirus, coronavirus and picornavirus in bats and co-infection of viruses from different families, Bats and Emerging Infectious Diseases Workshop. 2009.

Zhu H., Wang J., Wang P., Song W., Zheng Z., Chen R., Guo K., Zhang T., Peiris J.S.M., Chen H. and Guan Y., Substitution of lysine at 627 position in PB2 protein does not change virulence of the 2009 pandemic H1N1 virus in mice, Virology. 2010, 401: 1-5.

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