My laboratory focuses on the pathogenic interplay of the HIV-1 and HTLV-I human retroviruses with immune cells. Infection of human hosts with these retroviruses produces contrasting diseases within the CD4 subset of T lymphocytes, specifically the Acquired Immune Deficiency Syndrome (AIDS) with HIV-1 and the Adult T-cell Leukemia (ATL) with HTLV-1. Their studies explore the molecular biology of the HIV Vif, Nef and Vpr gene products as well as the transforming properties of HTLV-I Tax. More recently, we have begun to study HIV and HTLV-1 Env-mediated fusion and the mechanisms underlying transmission of HIV across the female genital mucosa.
We continue to also pursue our longstanding interest in the biology of the NF-kB/Rel family of transcription factors, which serve as "master regulators" of the immune and inflammatory responses. These studies currently focus on the role of these transcription factors as major antagonists of HIV latency.
Due to the broad scope of experimental questions, we employ a wide range of molecular, biochemical, cell biological and immunological techniques to study HIV and HTLV-I pathogenesis. Individuals completing training in the laboratory routinely acquire expertise in all of these areas. Increasingly, we are utilizing transgenesis and gene disruption approaches to study the function of specific genes in vivo. Our studies often take advantage of the outstanding core services offered at the Gladstone Institutes, including cores in Virology, Immunology, Genomics, Flow Cytometry, Microscopy, Histology, Transgenesis and Gene Disruption.
Geleziunas R, Xu W, Takeda K, Ichijo H, Greene WC. HIV-1 Nef inhibits ASK1-dependent death signaling providing a potential mechanism for protecting the infected host cell. Nature 410:834-838, 2001.
de Noronha CMC, Sherman MP, Lin HW, Cavrois MV, Moir RD, Goldman RD, Greene WC. Dynamic disruptions in nuclear envelope architecture and integrity induced by HIV-1 Vpr. Science 294:1105-1108, 2001.
Chen LF, Fischle W, Verdin E, Greene WC. Duration of nuclear NF-kB action is regulated by reversible acetylation. Science 293:1653-1657, 2001.
Greene WC, Peterlin BM. Charting HIV's remarkable voyage through the cell: Basic science as a passport to future therapy. Nat. Med. 8:673-680, 2002.
Chen LF, Mu Y, Greene WC. Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kB. EMBO J. 21:6539-6548, 2002.
Stopak K, de Noronha C, Yonemoto W, Greene WC. HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Mol. Cell 12:591-601, 2003.
Greene WC. The brightening future of HIV therapeutics. Nat. Immunol. 5:867-871, 2004.
Williams SA, Chen LF, Kwon H, Ruiz-Jarabo CM, Verdin E, Greene WC. NF-kappaB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation. EMBO J. 25:139-49, 2006
Cavrois M, Neidleman J, Kreisberg JF, Greene WC. In Vitro Derived Dendritic Cells Trans -infect CD4 T Cells Primarily with Surface-bound HIV-1 Virions. PLoS Path. 3:e4, 2007.
Soros VB, Yonemoto W, Greene WC. Newly synthesized APOBEC3G is incorporated into HIV virions, inhibited by HIV RNA, and subsequently activated by RNase H. PLoS Path. e:315, 2007
Greene WC. A history of AIDS: Looking back to see ahead. Eur. J. Immunol. 37:S94–102, 2007.
Williams SA, Kwon H, Chen L-F, Greene WC. Sustained induction of NF-kB is required for efficient expression of latent HIV-1. J. Virol. 81:6043–6056, 2007.
Chiu YL, Greene WC. The APOBEC3 cytidine deaminases: an innate defensive network opposing exogenous retroviruses and endogenous retroelements. Annu Rev Immunol. 26:317-353, 2008.
Cavrois M, Neidleman J, Greene WC. The Achilles heel of the Trojan horse model of HIV trans-infection. PLoS Path. 4:e1000051, 2008. PMCID: PMC2430767
Santiago ML, Montano M, Benitez R, Messer RJ, Yonemoto W, Chesebro B, Hasenkrug KJ, Greene WC. APOBEC3 encodes Rfv3, a gene influencing neutralizing antibody control of retrovirus infection. Science 321:1343–1346, 2008.
Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ. The challenge of finding a cure for HIV infection. Science 323:1304–1307, 2009.
Roan NR, Greene WC. A seminal finding for understanding HIV transmission. Cell 131:1044-1026, 2007.
Doitsh G, Cavrois M, Lassen KG, Zepeda O, Yang Z, Santiago ML, Hebbler AM, Greene WC. Abortive HIV infection mediates CD4 T-cell depletion and inflammation in human lymphoid tissue. Cell 143:789–801, 2010. PMCID: PMC3026834
Roan NR, Muller JA, Liu H, Chu S, Arnold F, Sturzel C, Walther P, Dong M, Witkowska E, Kirchhoff F, Munch F, Greene WC. Peptides released by physiological cleavage of semen coagulum proteins form amyloids that enhance HIV infection. Cell Host Microbe 10:541–550, 2011. PMCID: PMC3257029.
Chan J, Greene WC. Dynamic roles for NF-kB in HTLV-I and HIV-1 retroviral pathogenesis. Immunol. Rev. 246:286–310, 2012.
Lassen KG, Hebbeler AM, Bhattacharyya D, Lobritz MA, Greene WC. A flexible model of HIV-1 latency permitting evaluation of many primary CD4 T-cell reservoirs. PLoS One. 7:e30176, 2012. PMCID: PMC3265466.
Wissing S, Munoz-Lopez M, Macia A, Yang Z, Montano M, Collins W, Garcia-Perez JL, Moran JV, Greene WC. Reprogramming somatic cells into iPS cells activates LINE-1 retroelement mobility. Hum. Mol. Genetics 21:208–218, 2012. PMCID: PMC3235014.