antioxidants directly inhibit viral transcription

[Guest guest]

Department of Genetics, Stanford University School of Medicine, California 94305.

In

studies presented here, we demonstrate that antioxidants regulate

NF-kappa B activation and signal transduction pathways leading to HIV

expression. We show (1) that N-acetyl-L-cysteine (NAC), an antioxidant

and an efficient glutathione (GSH) precursor, inhibits NF-kappa B

activation and HIV expression under conditions in which GSH is depleted

and NAC cannot be converted to GSH, (2) that the D-stereoisomer of NAC

and a wide variety of chemically unrelated antioxidants also inhibit

NF-kappa B activation and/or transcription directed by the HIV LTR, and

(3) that depletion of GSH, the principal intracellular antioxidant,

augments HIV production in an acute infection model. Taken together,

these findings suggest direct antioxidant action as the mechanism for

inhibition of HIV transcription by NAC. They also confirm that GSH,

acting in its capacity as an antioxidant, regulates HIV expression and

that exogenous antioxidants can potentiate this regulation.

PMID: 8512745