N-acetylcysteine inhibits latent HIV expression in chronically infected cells.
The progression of the human immunodeficiency virus (HIV) infection from its early latent (asymptomatic) stage to active, late-stage acquired immunodeficiency syndrome (AIDS) apparently begins with the production of inflammatory cytokines that stimulate the expression and replication of the latent virus. We have shown that N-acetylcysteine, a cysteine precursor that is converted intracellularly into glutathione, blocks cytokine-stimulated HIV replication in an acutely infected T-cell line and in acutely infected peripheral blood mononuclear cells from normal individuals. In this report, we show that N-acetylcysteine also inhibits stimulated HIV expression in chronically infected monocyte and T-cell lines which are used as models for latent infection in AIDS. Furthermore, we show that N-acetylcysteine blocks viral production in monocyte cell lines more effectively than it blocks viral production in T cells. Since monocytes are a major reservoir for HIV in infected individuals, these results suggest that N-acetylcysteine may slow the change from latency to the later stages of AIDS in HIV-infected individuals.
Department of Genetics, Stanford University, CA 94305.
M
M
Roederer
P A
PA
Raju
F J
FJ
Staal
L A
LA
Herzenberg
L A
LA
Herzenberg
D000111:Acetylcysteine / Q000494:pharmacology*; D000998:Antiviral Agents; D002460:Cell Line; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D012367:RNA, Viral / Q000096:biosynthesis / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate; D000111:Acetylcysteine