The Human immunodeficiency virus type 1 (HIV-1) pandemic continues to drastically threaten the lives, welfare, and social stability of people worldwide. Global estimates indicate that roughly 15,000 new HIV infections occur each day, with one tenth of these occurring in children. Due to the drastic threat of this viral infection to human lives, extensive fundamental research efforts are continuingly needed to explore the molecular mechanisms underlying HIV-1 replication, dissemination and pathogenesis. The knowledge gained from these fundamental studies will lead to the development of new and effective preventative, and therapeutic strategies to help control the spread of HIV-1 infection.

Between the host and viral pathogens, there exists a balance between infection and health, were each side is in continual evolution to try and upset the equilibrium in favor of its desired outcome. The combat between host cells and viral invaders is an ancient one and continues today. Cells have evolved different mechanisms to protect themselves from viral pathogens. At the same time, viruses also developed their own ways to escape these innate inhibitory pathways. Both cells and viruses have devised numerous mechanisms of evasion and attenuation to impair one another. In addition, to carry out a successful infection, HIV-1 takes advantage of various host cellular proteins and cellular pathways during various steps of the HIV-1 life cycle. It is these mechanisms that science is now trying to understand and to explore as potential target for antiviral therapies. 

It is known that HIV-1 integrase contributes to different replication steps during early stage of HIV-1 infection, including reverse transcription,    nuclear import, chromatin targeting and integration. Even though numbers of cellular factors have been identified to be integrase¡¯s cofactors and we have gained much more knowledge for integrase¡¯s action, the exact mechanism(s) how integrase acts in these multiple steps is still not  fully understood.

APOBEC3G (A3G), a deoxycytidine deaminase, is a potent host antiviral factor that can restrict HIV-1 infection. During Vif-negative HIV-1 replication, A3G is able to incorporate into HIV-1 particles and acts to mutate reverse transcribed viral DNA, and to inhibit reverse transcription. However, its antiviral activity was blocked by HIV-1 Vif since this viral protein is able to induce A3G degradation and blocking its incorporation into the viral particle. Thus, how to enable A3G escaping from Vif¡¯s blockage and to rescue its potent antiviral activity is of considerable interest, as it may provide a possible novel therapeutic strategy for treating HIV-1 infection. 

In addition to HIV-1, the avian influenza H5N1 virus is another viral pathogen that threatens the human lives in the world. Between 2003 and June 2007, there were a total of 317 confirmed human cases of H5N1 viral infection, 191 of which were fatal, according to the World Health Organization. At present, even though H5N1 viruses are not readily transmissible between humans, it is quite possible that they can acquire such transmissibility via mutations and/or gene reassortment from circulating human influenza A viruses. Due to the high virulence of this virus, its endemic presence and its high mutational rate, there is an urgent need for developing new vaccine and novel drugs against this high-risk virus. Moreover, more detailed studies are necessary for better understanding how H5N1 avian influenza virus requires ability to target human cells, specially the primary human airway epithelium cells.

Research projects:

Project I. Investigation of molecular mechanisms underlying the early stage of HIV-1 replication, especially on HIV-1 integrase/cellular protein interactions required for HIV-1 DNA nuclear import, chromatin targeting and integration.

Project II. Study on the mechanism involved in the combat between HIV-1 Vif and host defenders during HIV-1 replication, and development of new antiviral strategies by using host anti-HIV molecules.

Project III. Development of new preventative and therapeutic strategies against HIV-1 infection and transmission.

Project IV.  Development of a safe and sensitive avian influenza virus entry system for studying of the impact of H5N1 HA mutations on virus entry in human cells and for screening antiviral agents.

Recent Publications:

1. Patel, A. K. Tran, M. Gray, T. Taylor, Y. Li, X-j Yao , H Feldmann, D. Kobasa and G.P. Kobinger. Evaluation of conserved and variable influenza antigens for immunization against different isolates of H5N1 viruses. Vaccine. 2009. (Accepted).
   
2. Lehmann, MG, Abrahamyan LG, Milev MP, X-J Yao , Pante N, and Mouland AJ. Intracellular Transport of HIV-1 genomic RNA is Dependent on Dynein and Late Endosomal Vesicles. J. Biol. Chem. Mar 13 [Epub ahead of print], 2009.
   
3. Oyugi J., F.C.M. Vouriot, J. Alimonti, S. Wayne, M. Luo, A. Land, Z-j AO, X-j Yao , R.P. Sekaly, L.J. Elliott, J.N Simonsen, T..B Ball, W. Jaoko, J. Kimani, F.A. Plummer and K.R. Fowke. A common CD4 gene variant is associated with a greater risk of HIV-1 infection in Kenyan female sex workers. J. Infect. Dis. Mar 16. [Epub ahead of print], 2009.
   
4. Xu Z-k, Y-F Zheng, Z-j Ao, M. Clement, A. Mouland, G.V Kalpana , .P Belhumeur, E.A. Cohen, and X-j Yao . Requirement of the chromatin binding region within the C-terminal catalytic core domain of HIV-1 integrase for the yeast lethality and viral replication. Retrovirology. 5(102)p1-15, 2008.
   
5. Liang B.B, M. Luo, T.B. Ball, X-j Yao , G Wilfred R. Cuff, Domselaar, M. Cheang, S. Jones, and F.A. Plummer. Systematic analysis of host immunological pressure on the envelope gene of human immunodeficiency virus type 1 by an immunobioinformatics approach. Curr HIV Res. 6(4):370-9, 2008.
   
6. Ao Z-j, Z Yu, L Wang, Y-f Zheng, and X-j Yao . Vpr14-88-Apobec3G fusion protein is efficiently incorporated into Vif-positive HIV-1 particles and inhibits viral replication. PLoS ONE . Apr 16;3(4):e1995 , 2008.
   
7. Ao Z-j, A. Patel, K. Tran, X-y He, K. Fowke, K. Coombs, D. Kobasa, G. Kobinger, and X-j. Yao . Characterization of a trypsin-dependent avian influenza H5N1 hemagglutinin pseudotyped HIV vector system and Screening for inhibitory peptides. Antiviral Research. 79:12-18 (Epub Mar 6), 2008.
   
8. Ao Z-j , G-y Huang, H. Yao, Z-k Xu, M. Labine, A. Cochrane, X-j Yao . Interaction of human immunodeficiency virus type 1 integrase with cellular nuclear import receptor importin 7 and its impact on viral replication. J Biol Chem. 2007, 282:13456-67.
   
9. Z-j Ao, K.R. Fowke, Éric A. Cohen and X-j Yao . Contribution of the C-terminal tri-lysine regions of HIV-1 integrase for efficient reverse transcription and viral DNA nuclear import Retrovirology. 2(62): 1-15, 2005.
   
10. X-J Yao , N. Rougeau, G. Duisit, J. Lemay and É.A. Cohen. Analysis of HIV-1 Vpr determinants responsible for cell growth arrest in Saccharomyces cerevisiae. Retrovirology. 1(12):1-11, 2004.
    
11. Z-j Ao, X-J Yao and E.A. Cohen Assessment of the Role of the Central DNA Flap in Human Immunodeficiency Virus Type 1 Replication using a Single-Cycle Replication System. J. Virol. 78:3170-3177, 2004.
    
12. Julian J.L., O.J. Cohen, Z-l Nie, J.G. Weaver, T.S. Gomez, X-J Yao, D. Lynch, A.A. Pilon, N. Hawley, J.E. Kim, Z-X Chen, M. Montpetit, J. Sanchez-Dardon, E.A. Cohen, and A.D. Badley. Vpr mutation R77Q is associated with long term non progressive HIV infection and an impaired ability to induce T cell depletion in vivo. J. Clin. Invest. 111: 1547-1554. 2003.

LOOKING FOR GRADUATE STUDENTS WITHIN THE NEXT YEAR

Looking for PostDoc fellow.  The previous research experience in molecular virology, especially on HIV molecular virology is preferable.