Cytokine-stimulated human immunodeficiency virus replication is inhibited by N-acetyl-L-cysteine.
We show that the stimulation of human immunodeficiency virus (HIV) brought about by tumor necrosis factor alpha and phorbol 12-myristate 13-acetate can be inhibited by adding N-acetyl-L-cysteine (NAC). NAC, which replenishes intracellular glutathione, effectively inhibits the tumor necrosis factor alpha- or phorbol ester-stimulated replication of HIV in acutely infected cell cultures. NAC also inhibits the cytokine-enhanced HIV long terminal repeat-directed expression of beta-galactosidase in in vitro HIV model systems. These results show that intracellular thiol levels influence HIV production. Furthermore, because NAC reverses tumor necrosis factor alpha toxicity both in cells and in animals and is a well-known drug that can be administered orally without known toxicity in humans, these results suggest that NAC is a possible therapeutic agent in AIDS.
Roederer
M
M
Department of Genetics, Stanford University, CA 94305.
Staal
F J
FJ
Raju
P A
PA
Ela
S W
SW
Herzenberg
L A
LA
Herzenberg
L A
LA
D000111:Acetylcysteine / Q000494:pharmacology*; D000998:Antiviral Agents; D002460:Cell Line; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D000998:Antiviral Agents; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D001616:beta-Galactosidase; D013755:Tetradecanoylphorbol Acetate; D000111:Acetylcysteine