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Bindong Liu PhD Affiliation: Meharry Medical College Microbiology and Immunology "HIV/AIDS","Infectious and Immunological Diseases" Title: Associate Professor Rank: Address: 5029 Hubbard Hospital BLDG 1005 Dr. D. B. Todd BLVD Nashville, TN 37208 Contact: Email: [email protected] Telephone: 615-327-6877 Narrative The research in our lab focuses on delineating the interactions between HIV-1 and host, as well as HIV-1 and other human microbes with the effort on finding a solution to inhibit HIV-1 replication. We have following three ongoing projects. 1. Mucosal surfaces serve as the predominant point of transmission for human immunodeficiency virus (HIV-1). However, it is well-documented that the transmission/acquisition of HIV-1 through orogenital contact is rare. The risk associated with the vaginal acquisition of HIV-1 after sexual contact with a HIV-1 positive individual is 0.03% to 0.2%, while the risk of oral acquisition is estimated to be 20 times less. This indicates that the protection provided by the innate and adaptive immune system of the host is robust, but varies according to the mucosal site. APOBEC3G (A3G) is a potent host restriction factor of HIV-1. It has been shown that A3G blocks HIV-1 replication or transmission when its expression is up-regulated. Streptococcus Cristatus CC5A is a non-pathogenic oral bacterial. We found that a small molecule of Streptococcus cristatus CC5A (S. cristatus CC5A) was able to upregulate APOBEC3G expression and inhibit HIV replication. Now we are working on developing a novel, efficient anti-HIV/AIDS strategy using this molecule. 2. GB virus type C (GBV-C, also called hepatitis G virus) is a single, positive strand RNA virus in the Flaviviridae family. It has not been conclusively associated with any known disease, although it is a very common infection in humans. Most of the cohort studies about the interaction of GBV-C and HIV-1 showed that GBV-C infection could prolong AIDS patient survival. Since GBV-C shares the same transmission pathway with HIV-1 and replicates in CD4+ T cells, it could be a very promising candidate for establishing novel anti-AIDS therapy strategies and gene therapy vectors which specifically deliver anti-HIV genes to CD4+ T cells. In our study, we found that when one of GBV-C structural protein E2 was co-expressed with the HIV-1 proviral construct, HIV-1 Gag processing was dramatically inhibited resulting less virus has been released. This may shed light on developing GBV-C as novel anti-HIV/AIDS strategy. We are working on elucidating the mechanism of GBV-C’s antiHIV/AIDS effect and testing whether we could develop a novel anti-HIV/AIDS drug based on this discovery. 3. We are trying to understand the interaction between HIV-1 Vif and APOBEC3G (A3G). A3G is a host restriction factor of HIV-1. HIV encodes Vif to overcome A3G antiviral effect. It is well-established that Vif counteracts A3G via proteasome-mediated A3G degradation and repression of A3G translation. Such a mechanism is essential for the production of infectious virions because inclusion of A3G in Vifdeficient virions has been shown to result in non-infectious particles. However, clinical and laboratory evidence, including that of our group, has shown that A3G is detectable in Vif competent HIV-1 viral particles without affecting their infectivity. How HIV solves this conundrum remains unclear. We have been addressing the above paradox by examining A3G activities in the presence of Vif. We showed that besides depleting A3G, Vif directly inhibits A3G cytidine deaminase activity, which is necessary for G-to-A hypermutation in an exogenous protein expression system. As a result, the presence of functional Vif significantly reduces the rate of G-to-A hypermutations generated by A3G to promote HIV replication. Right now we are further evaluating this phenotype under physiologically relevant condition and working on the identification of the specific interaction domains which play a role in inhibiting A3G cytidine deaminase activity. Understanding details of the interaction between APOBEC and HIV-1 Vif will shed light on anti-HIV/AIDS drug design. Other Positions Title Director Institution Meharry Medical College Department Division BSL3 and FACS Core Title Associate Professr Institution Meharry Medical College Department Division Center for AIDS Health Disparities Research Title Associate Director Institution Tennessee Center for AIDS Research Department Division Laboratory Science Core Awards and Honors 1993 Heilongjiang Province - Third Place: Outstanding Paper on Science and Technology 1995 Equine Infectious Anemia (EIA) - National Science and Technology Progress Award Publications 1. Wang Y, Kinlock BL, Shao Q, Turner TM, Liu B. HIV-1 Vif inhibits G to A PubMed hypermutations catalyzed by virus-encapsidated APOBEC3G to maintain HIV-1 infectivity. Retrovirology. 2014; 11:89. 2. Wang Z, Luo Y, Shao Q, Kinlock BL, Wang C, Hildreth JE, Xie H, Liu B. Heat-Stable PubMed Molecule Derived from Streptococcus cristatus Induces APOBEC3 Expression and Inhibits HIV-1 Replication. PLoS One. 2014; 9(8):e106078. 3. Kinlock BL, Wang Y, Turner TM, Wang C, Liu B. Transcytosis of HIV-1 through PubMed Vaginal Epithelial Cells Is Dependent on Trafficking to the Endocytic Recycling Pathway. PLoS One. 2014; 9(5):e96760. 4. Song M, Chen D, Lu B, Wang C, Zhang J, Huang L, Wang X, Timmons CL, Hu J, Liu B, PubMed Wu X, Wang L, Wang J, Liu H. PTEN loss increases PD-L1 protein expression and affects the correlation between PD-L1 expression and clinical parameters in colorectal cancer. PLoS One. 2013; 8(6):e65821. 5. Timmons CL, Shao Q, Wang C, Liu L, Liu H, Dong X, Liu B. GB virus type C E2 protein PubMed inhibits human immunodeficiency virus type 1 assembly through interference with HIV-1 gag plasma membrane targeting. J Infect Dis. 2013 Apr; 207(7):1171-80. 6. Dey A, Mantri CK, Pandhare-Dash J, Liu B, Pratap S, Dash C. Downregulation of PubMed APOBEC3G by xenotropic murine leukemia-virus related virus (XMRV) in prostate cancer cells. Virol J. 2011; 8:531. 7. Wang Y, Shao Q, Yu X, Kong W, Hildreth JE, Liu B. N-terminal hemagglutinin tag PubMed renders lysine-deficient APOBEC3G resistant to HIV-1 Vif-induced degradation by reduced polyubiquitination. J Virol. 2011 May; 85(9):4510-9. 8. Shao Q, Wang Y, Hildreth JE, Liu B. Polyubiquitination of APOBEC3G is essential for PubMed its degradation by HIV-1 Vif. J Virol. 2010 May; 84(9):4840-4. 9. Tie Y, Liu B, Fu H, Zheng X. Circulating miRNA and cancer diagnosis. Sci China C Life PubMed Sci. 2009 Dec; 52(12):1117-22. 10. Moorman J, Zhang Y, Liu B, LeSage G, Chen Y, Stuart C, Prayther D, Yin D. HIV-1 PubMed gp120 primes lymphocytes for opioid-induced, beta-arrestin 2-dependent apoptosis. Biochim Biophys Acta. 2009 Aug; 1793(8):1366-71. 11. Wang T, Zhang W, Tian C, Liu B, Yu Y, Ding L, Spearman P, Yu XF. Distinct viral PubMed determinants for the packaging of human cytidine deaminases APOBEC3G and APOBEC3C. Virology. 2008 Jul 20; 377(1):71-9. 12. Xu Y, Xu G, Liu B, Gu G. Cre reconstitution allows for DNA recombination selectively PubMed in dual-marker-expressing cells in transgenic mice. Nucleic Acids Res. 2007; 35(19):e126. 13. Wang T, Tian C, Zhang W, Luo K, Sarkis PT, Yu L, Liu B, Yu Y, Yu XF. 7SL RNA mediates PubMed virion packaging of the antiviral cytidine deaminase APOBEC3G. J Virol. 2007 Dec; 81(23):13112-24. 14. Luo K, Wang T, Liu B, Tian C, Xiao Z, Kappes J, Yu XF. Cytidine deaminases PubMed APOBEC3G and APOBEC3F interact with human immunodeficiency virus type 1 integrase and inhibit proviral DNA formation. J Virol. 2007 Jul; 81(13):7238-48. 15. Wang J, Shackelford JM, Casella CR, Shivers DK, Rapaport EL, Liu B, Yu XF, Finkel TH. PubMed The Vif accessory protein alters the cell cycle of human immunodeficiency virus type 1 infected cells. Virology. 2007 Mar 15; 359(2):243-52. 16. Luo K, Xiao Z, Ehrlich E, Yu Y, Liu B, Zheng S, Yu XF. Primate lentiviral virion infectivity PubMed factors are substrate receptors that assemble with cullin 5-E3 ligase through a HCCH motif to suppress APOBEC3G. Proc Natl Acad Sci U S A. 2005 Aug 9; 102(32):114449. 17. Liu B, Sarkis PT, Luo K, Yu Y, Yu XF. Regulation of Apobec3F and human PubMed immunodeficiency virus type 1 Vif by Vif-Cul5-ElonB/C E3 ubiquitin ligase. J Virol. 2005 Aug; 79(15):9579-87. 18. Luo K, Liu B, Xiao Z, Yu Y, Yu X, Gorelick R, Yu XF. Amino-terminal region of the PubMed human immunodeficiency virus type 1 nucleocapsid is required for human APOBEC3G packaging. J Virol. 2004 Nov; 78(21):11841-52. 19. Liu B, Yu X, Luo K, Yu Y, Yu XF. Influence of primate lentiviral Vif and proteasome PubMed inhibitors on human immunodeficiency virus type 1 virion packaging of APOBEC3G. J Virol. 2004 Feb; 78(4):2072-81. 20. Yu X, Yu Y, Liu B, Luo K, Kong W, Mao P, Yu XF. Induction of APOBEC3G PubMed ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science. 2003 Nov 7; 302(5647):1056-60. 21. Kong W, Tian C, Liu B, Yu XF. Stable expression of primary human immunodeficiency PubMed virus type 1 structural gene products by use of a noncytopathic sindbis virus vector. J Virol. 2002 Nov; 76(22):11434-9. 22. Yu XF, Liu W, Chen J, Kong W, Liu B, Zhu Q, Liang F, McCutchan F, Piyasirisilp S, Lai S. PubMed Maintaining low HIV type 1 env genetic diversity among injection drug users infected with a B/C recombinant and CRF01_AE HIV type 1 in southern China. AIDS Res Hum Retroviruses. 2002 Jan 20; 18(2):167-70. 23. Qiu JT, Liu B, Tian C, Pavlakis GN, Yu XF. Enhancement of primary and secondary PubMed cellular immune responses against human immunodeficiency virus type 1 gag by using DNA expression vectors that target Gag antigen to the secretory pathway. J Virol. 2000 Jul; 74(13):5997-6005. 24. Liu B, Dai R, Tian CJ, Dawson L, Gorelick R, Yu XF. Interaction of the human PubMed immunodeficiency virus type 1 nucleocapsid with actin. J Virol. 1999 Apr; 73(4):2901-8. THANK YOU FOR USING THE RTRN RESEARCH COLLABORATION AND PROFESSIONAL NETWORKING SERVICE. RTRN Data Coordinating Center Mississippi e-Center @ Jackson State University 1230 Raymond Road, Box 1800, Jackson, Mississippi 39204 Phone: 601-979-0332, Fax: 601-979-0338, e-mail: [email protected]