Sodium butyrate stimulation of HIV-1 gene expression: A novel mechanism of induction independent of NF-κB

M. A. Laughlin, G. Y. Chang, J. W. Oakes, F. Gonzalez-Scarano, R. J. Pomerantz

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Nuclear factor kappa B (NF-κB) 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-α) 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-κB 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-κB-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-κB, as compared with PMA, which induces NF-κB 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 vital gene expression in these cells.

Original languageEnglish (US)
Pages (from-to)332-339
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Volume9
Issue number4
StatePublished - 1995

Keywords

  • Chromatin structure
  • HIV-1 latency
  • Sodium butyrate

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

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