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 role in stimulating human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-directed viral gene expression. We have previously described a cell line (TE671/RD) that fails to respond to phorbol myristate acetate (PMA) or tumor necrosis factor-alpha (TNF-alpha) in terms of amplifying HIV-1 LTR-driven gene expression unless it is concurrently 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-specific transcriptional factor with its target. We now show that these cells are in fact capable of inducing a free nuclear NF-kappa B-binding activity when stimulated with PMA but not when treated with sodium butyrate 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 cells with sodium butyrate is not blocked by N-acetylcysteine, whereas that of PMA stimulation is blocked. These observations are discussed in the context of a model where chromatin structure participates in the maintenance of restricted HIV-1 viral gene expression in these cells.
Laughlin
M A
MA
Dorrance H. Hamilton Laboratories, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Chang
G Y
GY
Oakes
J W
JW
Gonzalez-Scarano
F
F
Pomerantz
R J
RJ
D000111:Acetylcysteine / Q000494:pharmacology; D015152:Blotting, Northern; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects*; D016328:NF-kappa B / Q000502:physiology*; D012091:Repetitive Sequences, Nucleic Acid; D014775:Virus Activation / Q000187:drug effects
D002087:Butyrates; D016328:NF-kappa B; D020148:Butyric Acid; D000111:Acetylcysteine