1: EMBO J. 1998 Jun 1;17(11):3124-34. 

Modulation of cytokine-induced HIV gene expression by competitive binding of
transcription factors to the coactivator p300.

Hottiger MO, Felzien LK, Nabel GJ.

Howard Hughes Medical Institute, University of Michigan Medical Center, Ann
Arbor, MI 48109-0650, USA.

The host response to viral infection involves the secretion of multiple
cytokines which alter immune function and viral replication. These proteins
activate several signal transduction pathways in infected cells which must be
integrated to regulate cellular and viral gene expression. In this report, we
demonstrate that specific transcription factors induced by distinct cytokines
regulate HIV transcription by competitive binding to the p300 coactivator.
Interferon-alpha (IFN-alpha) was found to inhibit NF-kappaB-dependent HIV gene
expression stimulated by tumor necrosis factor-alpha (TNF-alpha). This
inhibition was mediated by binding of the IFN-alpha signal transducer and
activator of transcription 2, Stat2, to a specific domain of p300 which also
binds to the RelA (p65) subunit of NF-kappaB. p300 was found to be limiting with
respect to RelA (p65) and Stat2, and this effect was reversed by overexpression
of p300. Inhibition by Stat2 was specific for NF-kappaB and was not mediated by
Stat1, which is also induced by IFN-alpha. Gene activation induced by the Stat2
transcription domain was also inhibited by expression of RelA. These results
demonstrate that HIV transcription can be regulated in the nucleus by
competitive binding of specific cytokine-induced transcription factors to a
discrete domain of a transcriptional coactivator.

PMID: 9606194 [PubMed - indexed for MEDLINE]


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