Serum Vpr regulates productive infection and latency of human immunodeficiency virus type 1.
In human immunodeficiency virus (HIV)-positive individuals, the vast majority of infected peripheral blood cells and lymph node cells may be latently or nonproductively infected. The vpr open reading frame of HIV-1 encodes a 15-kDa virion-associated protein, Vpr. The vpr gene has been shown to increase virus replication in T cells and monocyte/macrophages in vitro. We have previously reported that vpr expression in various tumor lines leads to growth inhibition and differentiation, indicating that Vpr may function as a regulator of cellular permissiveness to HIV replication. Here we show that Vpr protein is present in significant amounts in the serum of AIDS patients. Purified serum Vpr activated virus expression from five latently infected cell lines, U1, OM.10.1, ACH-2, J1.1, and LL58. Serum Vpr also activated virus expression from resting peripheral blood mononuclear cells of HIV-infected individuals. Together, these findings implicate serum Vpr in the activation of HIV replication in vivo and in the control of latency. Anti-Vpr antibodies inhibited Vpr activity, suggesting that humoral immunity modulates Vpr activity in vivo. These results have broad implications for the virus life cycle and for the prospective control of HIV replication and pathogenesis.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104.
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Levy
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Y
Refaeli
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MacGregor
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Weiner
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000134:cerebrospinal fluid / Q000382:microbiology; D000595:Amino Acid Sequence; D016336:Gene Products, vpr / Q000097:blood / Q000134:cerebrospinal fluid / Q000502:physiology*; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000382:microbiology*; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D010455:Peptides; D054325:vpr Gene Products, Human Immunodeficiency Virus