Activation of human immunodeficiency virus type 1 in monocytoid cells by the protozoan parasite Leishmania donovani.
In this study, we demonstrated that the protozoan parasite Leishmania donovani and one of its major surface molecules, the lipophosphoglycan (LPG), can induce human immunodeficiency virus type 1 (HIV-1) expression in U1 and OM-10.1, two cell lines of monocytoid origin latently infected with HIV-1. Treatment of U1 cells with various concentrations of LPG (1, 5, and 10 microM) resulted in a dose-dependent secretion of tumor necrosis factor alpha (TNF-alpha). Suppression of LPG-induced HIV-1 expression by polyclonal anti-TNF-alpha antibodies further confirmed the involvement of this cytokine. Results from these studies indicate that the protozoan parasite L. donovani can induce the secretion of TNF-alpha that will function in an autocrine or paracrine manner to upregulate HIV-1 expression. Our data suggest for the first time that this protozoan parasite can be viewed as a potential cofactor in the pathogenesis of AIDS.
D000163:Acquired Immunodeficiency Syndrome / Q000503:physiopathology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D006028:Glycosphingolipids / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D007893:Leishmania donovani / Q000502:physiology*; D009000:Monocytes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology; D014775:Virus Activation / Q000187:drug effects; D017735:Virus Latency
D000906:Antibodies; D006028:Glycosphingolipids; D014409:Tumor Necrosis Factor-alpha; C008290:lipophosphonoglycan; D013755:Tetradecanoylphorbol Acetate