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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.
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