Modulatory effect of N-acetyl-L-cysteine on the HIV-1 multiplication in chronically and acutely infected cell lines.
N-acetyl-L-cysteine (NAC) is known to antagonize the PMA- or cytokine-stimulated HIV-1 replication in latently and acutely infected monocytic and lymphocytic cell lines, and to reduce the virus multiplication in acutely infected, PHA-stimulated PBMC. We here report on the modulatory effects of NAC on the HIV-1 multiplication in both chronically and acutely infected lymphocytes that produce high virus levels independently from cytokine activation. In both cases, NAC doses of 0.12 and 0.25 mM decreased, whereas doses of 0.5-2 mM increased the infectious HIV-1 yield. At these concentrations, the modulatory effect of NAC on the HIV-1 multiplication paralleled that on cell proliferation, suggesting a close correlation between the two phenomena; in fact, under conditions where NAC could not modulate the cell growth, the drug also failed to modulate the HIV-1 multiplication. High NAC concentrations (4-16 mM), which were able to increase the proliferative rate of both chronically infected H9/IIIB and normal T lymphocytes, increased up to 6-fold the virus multiplication in H9/IIIB cells but were inhibitory to HIV-1 in acutely infected cells. This inhibition was due to the fact that, like dextran sulfate, NAC interfered with an early event in the virus growth cycle. The finding that high NAC doses were also capable of preventing syncytium formation in H9/IIIB and C8166 (or MT-4) cocultures further indicated an interference of the drug with receptor-binding-related events.
Pani
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Dipartimento di Biologia Sperimentale, Universitä di Cagliari, Italy.
Marongiu
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ME
La Colla
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D000111:Acetylcysteine / Q000494:pharmacology*; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000998:Antiviral Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002459:Cell Fusion / Q000502:physiology; D002460:Cell Line; D016264:Dextran Sulfate / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D008221:Lymphoid Tissue / Q000166:cytology / Q000382:microbiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000382:microbiology*; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology
D000998:Antiviral Agents; D015215:Zidovudine; D016264:Dextran Sulfate; D000111:Acetylcysteine