ANTIOXIDANTS INHIBIT STIMULATION OF HIV TRANSCRIPTION

In studies presented here, we demonstrate that antioxidants regulate N F-kappaB activation and signal transduction pathways leading to HIV ex pression. We show (1) that N-acetyl-L-cysteine (NAC), an antioxidant a nd an efficient glutathione (GSH) precursor, inhibits NF-kappaB activa tion 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-k appaB activation and/or transcription directed by the HIV LTR, and (3) that depletion of GSH, the principal intracellular antioxidant, augme nts HIV production in an acute infection model. Taken together, these findings suggest direct antioxidant action as the mechanism for inhibi tion of HIV transcription by NAC. They also confirm that GSH, acting i n its capacity as an antioxidant, regulates HIV expression and that ex ogenous antioxidants can potentiate this regulation.