Substance P enhances HIV-1 replication in latently infected human immune cells.
Substance P (SP) is a potent modulator of neuroimmunoregulation. SP receptors are present on human monocytes and T lymphocytes, and SP alters the function of these immune cells. We investigated the effects of SP on HIV-1 replication in latently infected human immune cells. SP significantly enhanced HIV-1 replication in the latently infected promonocytic cell line (U1) and T lymphocyte line (ACH-2) stimulated with tumor necrosis factor (TNF-alpha). When added to these cells in combination with TNF-alpha, SP also enhanced HIV-1 gag gene expression in U1 and ACH-2 cells. This stimulatory effect of SP was associated with the activation of HIV-LTR (long terminal repeat) driven chloramphenicol acetyltransferase (CAT) gene expression, and could be blocked by pretreatment of U1 and ACH-2 cells with an SP receptor antagonist RP-67,580, indicating specific SP receptor-mediated regulation. Furthermore, the addition of SP to the cultures of latently infected peripheral blood mononuclear cells isolated from HIV-1-infected patients enhanced HIV-1 gag gene expression. Thus, SP may play a potentially important role as a positive regulator of HIV-1 replication in latently infected monocytes and lymphocytes. These observations may have significant implications toward understanding the role of neuropeptide SP in the immunopathogenesis of HIV-1 infection and AIDS.
Li
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Division of Immunologic and Infectious Diseases, The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Douglas
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SD
Song
L
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Sun
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Ho
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WZ
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics; D015658:HIV Infections / Q000276:immunology*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D015213:Neuroimmunomodulation / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D018040:Receptors, Neurokinin-1 / Q000235:genetics; D013373:Substance P / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
D000970:Antineoplastic Agents; D002273:Carcinogens; D015683:Gene Products, gag; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate