The human immunodeficiency virus type 1 vpr gene prevents cell proliferation during chronic infection. (original) (raw)
- Journal List
- J Virol
- v.69(2); 1995 Feb
- PMC188655
J Virol. 1995 Feb; 69(2): 882–888.
Program in Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Abstract
Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that can cause extensive cytopathicity in T cells. However, long-term productive infection of T-cell lines has been described. Here we show that although Vpr has no effect on the initial cytopathic effect of HIV-1, viruses that contain an intact vpr gene are unable to establish a chronic infection of T cells. However, virus with a mutated vpr gene can readily establish such long-term cultures. The effect of Vpr is independent of the env gene and the nef gene. Furthermore, expression of Vpr alone affects the progression of cells in the cell cycle. These results suggest that HIV-1 has evolved a viral gene to prevent chronic infection of T cells.
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Selected References
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- Adams M, Sharmeen L, Kimpton J, Romeo JM, Garcia JV, Peterlin BM, Groudine M, Emerman M. Cellular latency in human immunodeficiency virus-infected individuals with high CD4 levels can be detected by the presence of promoter-proximal transcripts. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3862–3866. [PMC free article] [PubMed] [Google Scholar]
- Bauer KD. Analysis of proliferation-associated antigens. Methods Cell Biol. 1990;33:235–247. [PubMed] [Google Scholar]
- Boise LH, González-García M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nuñez G, Thompson CB. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell. 1993 Aug 27;74(4):597–608. [PubMed] [Google Scholar]
- Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L, Lewis P, Goldfarb D, Emerman M, Stevenson M. A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature. 1993 Oct 14;365(6447):666–669. [PMC free article] [PubMed] [Google Scholar]
- Bukrinsky MI, Stanwick TL, Dempsey MP, Stevenson M. Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection. Science. 1991 Oct 18;254(5030):423–427. [PMC free article] [PubMed] [Google Scholar]
- Cameron PU, Pope M, Gezelter S, Steinman RM. Infection and apoptotic cell death of CD4+ T cells during an immune response to HIV-1-pulsed dendritic cells. AIDS Res Hum Retroviruses. 1994 Jan;10(1):61–71. [PubMed] [Google Scholar]
- Chalfie M, Tu Y, Euskirchen G, Ward WW, Prasher DC. Green fluorescent protein as a marker for gene expression. Science. 1994 Feb 11;263(5148):802–805. [PubMed] [Google Scholar]
- Chen C, Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. [PMC free article] [PubMed] [Google Scholar]
- Cohen EA, Dehni G, Sodroski JG, Haseltine WA. Human immunodeficiency virus vpr product is a virion-associated regulatory protein. J Virol. 1990 Jun;64(6):3097–3099. [PMC free article] [PubMed] [Google Scholar]
- De Rossi A, Ometto L, Roncella S, D'Andrea E, Menin C, Calderazzo F, Rowe M, Ferrarini M, Chieco-Bianchi L. HIV-1 induces down-regulation of bcl-2 expression and death by apoptosis of EBV-immortalized B cells: a model for a persistent "self-limiting" HIV-1 infection. Virology. 1994 Jan;198(1):234–244. [PubMed] [Google Scholar]
- Embretson J, Zupancic M, Ribas JL, Burke A, Racz P, Tenner-Racz K, Haase AT. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature. 1993 Mar 25;362(6418):359–362. [PubMed] [Google Scholar]
- Freed EO, Martin MA. HIV-1 infection of non-dividing cells. Nature. 1994 May 12;369(6476):107–108. [PubMed] [Google Scholar]
- Heinzinger NK, Bukrinsky MI, Haggerty SA, Ragland AM, Kewalramani V, Lee MA, Gendelman HE, Ratner L, Stevenson M, Emerman M. The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7311–7315. [PMC free article] [PubMed] [Google Scholar]
- Hoxie JA, Alpers JD, Rackowski JL, Huebner K, Haggarty BS, Cedarbaum AJ, Reed JC. Alterations in T4 (CD4) protein and mRNA synthesis in cells infected with HIV. Science. 1986 Nov 28;234(4780):1123–1127. [PubMed] [Google Scholar]
- Kimpton J, Emerman M. Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated beta-galactosidase gene. J Virol. 1992 Apr;66(4):2232–2239. [PMC free article] [PubMed] [Google Scholar]
- Kowalski M, Bergeron L, Dorfman T, Haseltine W, Sodroski J. Attenuation of human immunodeficiency virus type 1 cytopathic effect by a mutation affecting the transmembrane envelope glycoprotein. J Virol. 1991 Jan;65(1):281–291. [PMC free article] [PubMed] [Google Scholar]
- Laurent-Crawford AG, Krust B, Muller S, Rivière Y, Rey-Cuillé MA, Béchet JM, Montagnier L, Hovanessian AG. The cytopathic effect of HIV is associated with apoptosis. Virology. 1991 Dec;185(2):829–839. [PubMed] [Google Scholar]
- Lavallée C, Yao XJ, Ladha A, Göttlinger H, Haseltine WA, Cohen EA. Requirement of the Pr55gag precursor for incorporation of the Vpr product into human immunodeficiency virus type 1 viral particles. J Virol. 1994 Mar;68(3):1926–1934. [PMC free article] [PubMed] [Google Scholar]
- Levy DN, Fernandes LS, Williams WV, Weiner DB. Induction of cell differentiation by human immunodeficiency virus 1 vpr. Cell. 1993 Feb 26;72(4):541–550. [PubMed] [Google Scholar]
- Lu YL, Spearman P, Ratner L. Human immunodeficiency virus type 1 viral protein R localization in infected cells and virions. J Virol. 1993 Nov;67(11):6542–6550. [PMC free article] [PubMed] [Google Scholar]
- Lu YY, Koga Y, Tanaka K, Sasaki M, Kimura G, Nomoto K. Apoptosis induced in CD4+ cells expressing gp160 of human immunodeficiency virus type 1. J Virol. 1994 Jan;68(1):390–399. [PMC free article] [PubMed] [Google Scholar]
- Martin SJ, Matear PM, Vyakarnam A. HIV-1 infection of human CD4+ T cells in vitro. Differential induction of apoptosis in these cells. J Immunol. 1994 Jan 1;152(1):330–342. [PubMed] [Google Scholar]
- McConkey DJ, Hartzell P, Nicotera P, Wyllie AH, Orrenius S. Stimulation of endogenous endonuclease activity in hepatocytes exposed to oxidative stress. Toxicol Lett. 1988 Aug;42(2):123–130. [PubMed] [Google Scholar]
- Meltzer MS, Gendelman HE. Mononuclear phagocytes as targets, tissue reservoirs, and immunoregulatory cells in human immunodeficiency virus disease. Curr Top Microbiol Immunol. 1992;181:239–263. [PubMed] [Google Scholar]
- Mustafa F, Robinson HL. Context-dependent role of human immunodeficiency virus type 1 auxiliary genes in the establishment of chronic virus producers. J Virol. 1993 Nov;67(11):6909–6915. [PMC free article] [PubMed] [Google Scholar]
- Page KA, Landau NR, Littman DR. Construction and use of a human immunodeficiency virus vector for analysis of virus infectivity. J Virol. 1990 Nov;64(11):5270–5276. [PMC free article] [PubMed] [Google Scholar]
- Pantaleo G, Graziosi C, Demarest JF, Butini L, Montroni M, Fox CH, Orenstein JM, Kotler DP, Fauci AS. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature. 1993 Mar 25;362(6418):355–358. [PubMed] [Google Scholar]
- Paxton W, Connor RI, Landau NR. Incorporation of Vpr into human immunodeficiency virus type 1 virions: requirement for the p6 region of gag and mutational analysis. J Virol. 1993 Dec;67(12):7229–7237. [PMC free article] [PubMed] [Google Scholar]
- Pear WS, Nolan GP, Scott ML, Baltimore D. Production of high-titer helper-free retroviruses by transient transfection. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8392–8396. [PMC free article] [PubMed] [Google Scholar]
- Peden K, Emerman M, Montagnier L. Changes in growth properties on passage in tissue culture of viruses derived from infectious molecular clones of HIV-1LAI, HIV-1MAL, and HIV-1ELI. Virology. 1991 Dec;185(2):661–672. [PubMed] [Google Scholar]
- Popovic M, Sarngadharan MG, Read E, Gallo RC. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. [PubMed] [Google Scholar]
- Sodroski J, Goh WC, Rosen C, Campbell K, Haseltine WA. Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. Nature. 322(6078):470–474. [PubMed] [Google Scholar]
- Stevenson M, Haggerty S, Lamonica C, Mann AM, Meier C, Wasiak A. Cloning and characterization of human immunodeficiency virus type 1 variants diminished in the ability to induce syncytium-independent cytolysis. J Virol. 1990 Aug;64(8):3792–3803. [PMC free article] [PubMed] [Google Scholar]
- Temin HM. Mechanisms of cell killing/cytopathic effects by nonhuman retroviruses. Rev Infect Dis. 1988 Mar-Apr;10(2):399–405. [PubMed] [Google Scholar]
- Temin HM, Kassner VK. Replication of reticuloendotheliosis viruses in cell culture: chronic infection. J Gen Virol. 1975 Jun;27(3):267–274. [PubMed] [Google Scholar]
- Terai C, Kornbluth RS, Pauza CD, Richman DD, Carson DA. Apoptosis as a mechanism of cell death in cultured T lymphoblasts acutely infected with HIV-1. J Clin Invest. 1991 May;87(5):1710–1715. [PMC free article] [PubMed] [Google Scholar]
- Westervelt P, Henkel T, Trowbridge DB, Orenstein J, Heuser J, Gendelman HE, Ratner L. Dual regulation of silent and productive infection in monocytes by distinct human immunodeficiency virus type 1 determinants. J Virol. 1992 Jun;66(6):3925–3931. [PMC free article] [PubMed] [Google Scholar]
- Yao XJ, Garzon S, Boisvert F, Haseltine WA, Cohen EA. The effect of vpu on HIV-1-induced syncytia formation. J Acquir Immune Defic Syndr. 1993 Feb;6(2):135–141. [PubMed] [Google Scholar]
- Yuan X, Matsuda Z, Matsuda M, Essex M, Lee TH. Human immunodeficiency virus vpr gene encodes a virion-associated protein. AIDS Res Hum Retroviruses. 1990 Nov;6(11):1265–1271. [PubMed] [Google Scholar]
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