The human immunodeficiency virus type 1 vpr gene prevents cell proliferation during chronic infection

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.

[1]  H. Okayama,et al.  High-efficiency transformation of mammalian cells by plasmid DNA. , 1987, Molecular and cellular biology.

[2]  H. Temin Mechanisms of cell killing/cytopathic effects by nonhuman retroviruses. , 1988, Reviews of infectious diseases.

[3]  C. Thompson,et al.  bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death , 1993, Cell.

[4]  G. Nolan,et al.  Production of high-titer helper-free retroviruses by transient transfection. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[5]  H. Gendelman,et al.  Mononuclear phagocytes as targets, tissue reservoirs, and immunoregulatory cells in human immunodeficiency virus disease. , 1992, Current topics in microbiology and immunology.

[6]  K. Tanaka,et al.  Apoptosis induced in CD4+ cells expressing gp160 of human immunodeficiency virus type 1 , 1994, Journal of virology.

[7]  M. Emerman,et al.  A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells , 1993, Nature.

[8]  M. Chalfie,et al.  Green fluorescent protein as a marker for gene expression. , 1994, Science.

[9]  R. Steinman,et al.  Infection and apoptotic cell death of CD4+ T cells during an immune response to HIV-1-pulsed dendritic cells. , 1994, AIDS research and human retroviruses.

[10]  W. Paxton,et al.  Incorporation of Vpr into human immunodeficiency virus type 1 virions: requirement for the p6 region of gag and mutational analysis , 1993, Journal of virology.

[11]  J. Hoxie,et al.  Alterations in T4 (CD4) protein and mRNA synthesis in cells infected with HIV. , 1986, Science.

[12]  M. Emerman,et al.  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 , 1992, Journal of virology.

[13]  J. Sodroski,et al.  Attenuation of human immunodeficiency virus type 1 cytopathic effect by a mutation affecting the transmembrane envelope glycoprotein , 1991, Journal of virology.

[14]  F. Boisvert,et al.  The effect of vpu on HIV-1-induced syncytia formation. , 1993, Journal of acquired immune deficiency syndromes.

[15]  H. Robinson,et al.  Context-dependent role of human immunodeficiency virus type 1 auxiliary genes in the establishment of chronic virus producers , 1993, Journal of virology.

[16]  M. Matsuda,et al.  Human immunodeficiency virus vpr gene encodes a virion-associated protein. , 1990, AIDS research and human retroviruses.

[17]  D. Weiner,et al.  Induction of cell differentiation by human immunodeficiency virus 1 vpr , 1993, Cell.

[18]  Gilcher Ro Human retroviruses and AIDS. , 1988 .

[19]  D. Littman,et al.  Construction and use of a human immunodeficiency virus vector for analysis of virus infectivity , 1990, Journal of virology.

[20]  M. Emerman,et al.  Changes in growth properties on passage in tissue culture of viruses derived from infectious molecular clones of HIV-1LAI, HIV-1MAL, and HIV-1ELI. , 1991, Virology.

[21]  M P Dempsey,et al.  Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection. , 1991, Science.

[22]  R. F. Smith,et al.  Human retroviruses and aids, 1992 , 1992 .

[23]  K. Bauer Analysis of proliferation-associated antigens. , 1990, Methods in cell biology.

[24]  L. Ratner,et al.  Human immunodeficiency virus type 1 viral protein R localization in infected cells and virions , 1993, Journal of virology.

[25]  Seamus J. Martin,et al.  HIV-1 infection of human CD4+ T cells in vitro. Differential induction of apoptosis in these cells. , 1994, Journal of immunology.

[26]  Ashley T. Haase,et al.  Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS , 1993, Nature.

[27]  J. Sodroski,et al.  Human immunodeficiency virus vpr product is a virion-associated regulatory protein , 1990, Journal of virology.

[28]  S. Orrenius,et al.  Stimulation of endogenous endonuclease activity in hepatocytes exposed to oxidative stress. , 1988, Toxicology letters.

[29]  H. Temin,et al.  Replication of reticuloendotheliosis viruses in cell culture: chronic infection. , 1975, The Journal of general virology.

[30]  M. Emerman,et al.  HIV-1 infection of non-dividing cells , 1994, Nature.

[31]  Anthony S. Fauci,et al.  HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease , 1993, Nature.

[32]  M. Ferrarini,et al.  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. , 1994, Virology.

[33]  R. Gallo,et al.  Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. , 1984, Science.

[34]  J. Sodroski,et al.  Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity , 1986, Nature.

[35]  M. Emerman,et al.  HIV-1 INFECTION OF NON-DIVIDING CELLS. AUTHORS' REPLY , 1994 .

[36]  M. Stevenson,et al.  Cloning and characterization of human immunodeficiency virus type 1 variants diminished in the ability to induce syncytium-independent cytolysis , 1990, Journal of virology.

[37]  L. Montagnier,et al.  The cytopathic effect of HIV is associated with apoptosis. , 1991, Virology.

[38]  T. A. Hagan,et al.  Detection , Isolation , and Continuous Production of Cytopathic Retroviruses ( HTLV-III ) from Patients with AIDS and Pre-AIDS , 2022 .

[39]  W. Haseltine,et al.  Requirement of the Pr55gag precursor for incorporation of the Vpr product into human immunodeficiency virus type 1 viral particles , 1994, Journal of virology.

[40]  H. Gendelman,et al.  Dual regulation of silent and productive infection in monocytes by distinct human immunodeficiency virus type 1 determinants , 1992, Journal of virology.

[41]  D. Richman,et al.  Apoptosis as a mechanism of cell death in cultured T lymphoblasts acutely infected with HIV-1. , 1991, The Journal of clinical investigation.