SODIUM-BUTYRATE STIMULATION OF HIV-1 GENE-EXPRESSION - A NOVEL MECHANISM OF INDUCTION INDEPENDENT OF NF-KAPPA-B

Nuclear factor-kappa B (NF-kappa B) has been shown to play a central r ole in stimulating human immunodeficiency virus type 1 (HIV-1) long te rminal repeat (LTR)-directed viral gene expression. We have previously described a cell line (TE671/RD) that fails to respond to phorbol myr istate acetate (PMA) or tumor necrosis factor-alpha (TNF-alpha) in ter ms of amplifying HIV-1 LTR-driven gene expression unless it is concurr ently treated with sodium butyrate. It was not determined whether this lack of response stemmed from an inability of these cells to produce free NF-kappa B or from ineffectual interaction of this sequence-speci fic transcriptional factor with its target. We now show that these cel ls are in fact capable of inducing a free nuclear NF-kappa B-binding a ctivity when stimulated with PMA but not when treated with sodium buty rate alone. Furthermore, we show that sodium butyrate alone is equally potent in stimulating HIV-1 LTR-directed gene expression in latently infected U1 and ACH-2 cells in the absence of induction of nuclear NF- kappa B, as compared with PMA, which induces NF-kappa B activation in these cells. We also show that stimulation of HIV-1 expression in U1 c ells with sodium butyrate is not blocked by N-acetylcysteine, whereas that of PMA stimulation is blocked. These observations are discussed i n the context of a model where chromatin structure participates in the maintenance of restricted HIV-1 viral gene expression in these cells.