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.
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.
For a list of Dr. Yao's PubMed publications, please click here
1. Ao Z-j, 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. 2004, 78:3170-3177. (* corresponding authors)
2. Yao X-J, 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. 2004, 1(12): 1-11.
3. Ao Z-j, 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 2005, 2(62): 1-15.
4. 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.
5. 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 2008, 79:12-18.
6. 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. 2008, 6(4):370-9. IF 1.97
7. 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, 2008, 3(4):e1995.
8. 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. 2008, 5:p1-15. IF 6.47
9. Lehmann, MG, Abrahamyan LG, Milev MP, X-j Yao, Pante N, and Mouland AJ. Intracellular transport of human immunodeficiency virus type 1 genomic RNA and viral production are dependent on dynein motor function and late endosome positioning. J. Biol. Chem. 2009, 284:14572-85.
10. 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. 2009, 199:1327-34.
11. Patel A, Tran K, Gray M, Li Y, Ao Z, Yao X-j, Kobasa D, Kobinger GP. Evaluation of conserved and variable influenza antigens for immunization against different isolates of H5N1 viruses. Vaccine. 2009, 27:3083-9.
12. Awah FM, PN. Uzoegwu, JO. Oyugi, J. Rutherford, P. Ifeonu, X-j Yao, K. R. Fowke, MO. Eze. Free radical scavenging activity and immunomodulatory effect of Stachytarpheta angustifolia leaf extract. Food Chemistry. 2010, 119: 1409–1416.
13. Ji H-z, T.B. Ball, Z-j Ao, J. Kimani, X-j Yao, and F. Plummer. Reduced HIV-1 LTR transcription in subjects with protective IRF-1 polymorphisms: A potential mechanism mediating resistance to infection by HIV-1. Scandinavian Journal of Infectious Diseases. 2010, 42:389-94.
14. He, M-z, N. Yang, X-j Yao, C-l Sun and M. Yang. Modification and biological evaluation of novel 4-hydroxy-pyrone derivatives as non-peptidic HIV-1 protease inhibitors. Medicinal Chemistry Research. 2010, 20:200–209.
15. Ao, Z-j, K. Danappa Jayappa, M. Labine, Y-f Zheng, G. Kobinger, and X-j Yao*. Characterization of anti-HIV activity mediated by HIV-1 integrase C-terminal domain polypeptide expressed in susceptible cells. Journal of Antivirals and Antiretrovirals. 2010, 2:1 (20-28).
16. Zheng, Y-f., Z-j. Ao, K. Danappa Jayappa, and X-j Yao*. Characterization of HIV-1 Integrase’s Host Chromatin and LEDGF/p75 Binding Affinity by Mutagenesis Within Catalytic Core Domain of Integrase. Virology Journal. 2010, 7:68 (1-14), Epub March 23.
17. He, M-z, H. Zhang, X-j Yao, M. Eckart, E Zuo and M. Yang. Design, Biological Evaluation and SAR of Novel Pseudo-peptide Incorporating Benzheterocycles as HIV-1 Protease Inhibitors. Chemical Biology & Drug Design. 2010, 76:174–180.
18. Awah F., P. Uzoegwu, P. Ifeonu, J. Rutherford, X-j. Yao, F. Fehrmann, K. Fowke, A. Tsopmo, J. Oyugi, and M. Eze. Superoxide Anion Production in Phytohemagglutinin A and Staphylococcal Enterotoxin B-activated Human Peripheral Blood Mononuclear Cells. Nigerian Journal of Biochemistry and Molecular Biology. 2010, 25:18-24.
19. Ao, Z-J., K. Danappa Jayappa, B-C Wang, Y-F Zheng, S. Kung, E. Rassart, R. Depping, M. Kohler, EA. Cohen and X-j Yao*. Importin 3 interacts with HIV-1 integrase and is required for HIV-1 nuclear import and replication. Journal of Virology. 2010, 84:8650-8663.
20. Ao Z-j., X-X Wang, A. Bello, K. Danappa Jayappa, Z. Yu, X-Y He, K. Fowke, Xi Chen, J-h Li, G. Kobinger, and X-j Yao*. Characterization of the anti-HIV activity mediated by various R88-Apobec3G mutant fusion proteins in CD4+ T cells, PBMC and macrophages. Human Gene Therapy. 2011. 22:1225-37, Epub Mar 18.
21. Zheng Y-f., Z-j Ao, B- Wang, K Danappa Jayappa, and X-j Yao*. Host protein Ku70 binds and protects HIV-1 integrase from proteasomal degradation and is required for HIV replication. Journal of Biological Chemistry. 2011. 286:17722–17735.
22. Awah F.M., P.N. Uzoegwu, P. Ifeonu, J.O. Oyugi, J. Rutherford, X-j Yao, F. Fehrmann, K.R. Fowke, and M.O. Eze, Free radical scavenging activity, phenolic contents and cytotoxicity of selected Nigerian medicinal plants. Food Chemistry, 2011, 131:1279-1286.
23. Danappa Jayappa K., Z-j Ao, M. Yang, J-z Wang, and X-j Yao*. Identification of critical motifs in HIV-1 integrase required for Importin 3 interaction and its involvement in viral cDNA nuclear import. Journal of Molecular Biology. 2011, 410:847-862
24. Awah, FM., PN. Uzoegwu, P. Ifeonu, JO. Oyugi, J. Rutherford, X-J Yao, F. Fehrmann, KR. Fowke, and MO. Eze. Sphingomyelinase Inhibitory, and Free Radical Scavenging Potential of Selected Nigerian Medicinal Plant Extracts. Biokemistri . 2011; 23(3):129-135.
25. Patel A, Tran K, Gray M, Li Y, Yao X-j, Kobinger GP. Co-administration of certain DNA vaccine combinations expressing different H5N1 influenza virus antigens can be beneficial or detrimental to immune protection. Vaccine. 2011, 30:626-36.
26. Ao Z-j., K. Danappa Jayappa, B-c Wang, Y-f Zheng, X-x Wang, J-y Peng, and X-j Yao*, Contribution of Host Nucleoporin 62 in HIV-1 Integrase Chromatin Association and Viral DNA Integration. Journal of Biological Chemistry. 2012. 287:10544-55 (Epub Feb 03).
27. Wang X-x., Z-j Ao, L-y. Chen, G. Kobinger, J-y Peng, and X-j Yao*. Cellular antiviral protein Apobec3G specifically interacts with HIV-1 reverse transcriptase and inhibits its function during viral replication. Journal of Virology. 2012. 86:3777-86 (Epub Feb 01).
28. Danappa Jayappa, K, Z-j Ao, X-j Yao*, The HIV-1 passage from cytoplasm to nucleus: the process involving a complex exchange between the components of HIV-1 and cellular machinery to access nucleus and successful integration. International Journal of Biochemistry and Molecular Biology. 2012, 3(1):105-116.
29. C.M. Card, J.W. Rutherford, S. Ramdahin, X-j Yao, M. Kimani, C. Wachihi, J. Kimani, B Ball, FA. Plummer and K.R. Fowke. Reduced cellular susceptibility to in vitro HIV infection is associated with CD4+ T cell quiescence. PLoS ONE. 2012, 7(9):e45911
30. Fayaz M., Z-J Ao, M Girilal L-y Chen, X-z Xiao, P.T. Kalaichelvan and X-j Yao*. Inactivation of microbial infectiousness by silver nanoparticles coated condom: a new approach to inhibit HIV and HSV transmitted infection. International Journal of Nanomedicine. 2012, 7: 5007-5018.
31. Qiu X-g, G. Wong, L. Fernando, J. Ennis, J. Turner, J. Alimonti, X-j Yao, and G. Kobinger. Monoclonal antibodies combined with adenovirus-vectored interferon significantly extend the treatment window in Ebola virus-infected guinea pigs. Journal of Virology, 2013, 87:7754-7.
32. Chen L-y, Z-j Ao, K. Danappa Jayappa, G. Kobinger, S-p Liu, G-j Wu, M. Wainberg, and X-j Yao*. Characterization of antiviral activity of a benzamide derivative AH0109 against HIV-1 infection. Antimicrobial Agents and Chemotherapy. 2013 57:3547–3554.
33. Peng, J-y., Z-j. Ao, X-x Wang, C Mathew, S Ramdahin, X Chen, J-h Li, J-m He, B. Ball, K. Fowke, F. Plummer, J. Embree, and X-j Yao*. Naturally occurring Vif mutants derived from HIV-1 long-term survivors attenuate anti-APOBEC3G activity and viral replication in human T lymphocytes. Journal of Molecular Biology. 2013. 425,2840–2852
34. Y-f. Zheng, X-j Yao*, Posttranslational modifications of HIV-1 integrase by various cellular proteins during viral replication. Viruses, 2013, 5(7), 1787-1801
35. X-x Wang, Z-j Ao, K. Danappa Jayappa, Bei Shi, G. Kobinger and X-j Yao*.. R88-APOBEC3Gm inhibits the replication of both drug-resistant strains of HIV-1 and viruses produced from latently infected cells. Molecular Therapy - Nucleic Acids. 2014. 3, e151.
36. Z-j Ao, J Tang, W Chen, K Danappa Jayappa, and X-j Yao. Importin 1 interacts with HIV-1 integrase and plays a role in HIV-1 replication. Journal of Zunyi Med. University. 2014, 37:244-254.
37. K. Danappa Jayappa, K., Z-j Ao, X-x Wang, A. Mouland, S. Shekhar, Xi Yang, and X-j Yao* Human Immunodeficiency Virus Type 1 Employs the Cellular Dynein Light Chain 1 Protein for Reverse Transcription Through Interaction with its Integrase Protein. Journal of Virology 2015. 89(7):3497-511. IF
38. GA. Koumbadinga, N. Mahmood, L. Lei, W-g Cao, X-j Yao, S-t Zhang4 and J-y Xie. Control of Stability/Degradation of a Splicing Factor through Specific Lysines by Acetylation/Ubiquitination Pathways. BBA Gene Regulatory Mechanisms. 2015. 1849:1095-103.
39. R-C Su, A. Plesnarski, Z-j Ao, J. Kimani, A. Sivro, W. Jaoko, F.. Plummer, X-j Yao, and B. Ball. Reducing IRF-1 to levels observed in HESN subjects limits HIV replication, but not the extent of host immune activation. Mol. Therapy-Nucl. Acids 2015, 4:e259.
40. Z-j Ao, J. Huang, X-x Wang, X. Zhang, Q-g Ouyang, T. Tian, X-l Tan, and X-j Yao. Characterization of the single cycle replication of HIV-1 expressing Gaussia luciferase in human PBMCs, macrophages, and in CD4+ T cell-grafted nude mouse. Journal of Virological Methods. 2016. 228:95-102 (2015 Nov 27 [Epub ahead of print].
41. X. Zhang , Z-j Ao , A. Bello, X-z Ran , J. Wigle , G. Kobinger, and X-j Yao. Characterization of inhibitory effect of the extract of Prunella vulgaris against Ebola virus glycoprotein (GP)-mediated entry. Antiviral Research. 2016. 127: 20-31.
42. C-b Zhao , Z-j Ao and X-j Yao. Current advances in virus-like particles as a vaccination approach against HIV infection. Vaccines 2016. 2016, 4: 2
43. X-Z Ran, Z-J Ao, X-j Yao. Apobec3G-based Strategies to Defeat HIV Infection. Current HIV Researchh. 2016. 14:217-224
44. Tian T., Z-J Ao, X-x Wang, X-J Yao. Effect of several traditional Chinese medicines on the HIV-1 replication. Journal of Pathogen Biology (Chinese). 2016. 7:577
45. Z-j Ao, Zhu R., X-L Tan, Chen L-y,, S-p Liu, and X-j Yao. Activation of HIV-1 expression in latently infected CD4+ T cells by the small molecule PKC412. Virology Journal. 2016. 13:177.
46. B.D. Griffin, K. Muthuman3, B. Warner, A. Majer, M. Hagan, J. Audet1, D.R. Stein, C. Ranadheera, T. Racine, M. Vega, J. Pire, S. Kucas, K. N. Tran, K.L. Frost, C.D. Graff, G. Soule, L. Scharikow, J. Scott, G. McTavish, V. Smid, Y.K. Park, J.. Maslow, N.Y. Sardesai, J. Kim, X-J Yao, A. Bello, R, Lindsay, G. Boivin, S.A. Booth, D. Kobasa, C.E. Hyatt, D. Safronetz, D.B. Weiner, and G.P. Kobinger. DNA vaccination protects mice against Zika virus-induced damage to the testes. Nat. Commun. 2017 Jun 7;8:15743. doi: 10.1038/ncomms15743.
47. X-z Ran, Z-j Ao, A. Trajtman, W Xu, G. Kobinger, Y. Keynan, and X-j Yao. HIV-1 envelope glycoprotein stimulates viral transcription and increases the infectivity of the progeny virus through the manipulation of cellular machinery. Scientific Reports. 2017 (Accepted).
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.