Transactivator of transcription from HIV type 1 subtype E selectively inhibits TNF gene expression via interference with chromatin remodeling of the TNF locus

Shahin Ranjbar, Ricardo Rajsbaum Gorodezky, Anne E. Goldfeld

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The transactivator of transcription (Tat) protein is essential for efficient HIV type 1 (HIV-1) replication and is involved in the transcriptional regulation of the host immune response gene, TNF. In this study, we demonstrate that Tat proteins from representative HIV-1 subtype E isolates, but not from subtypes B or C, selectively inhibit TNF gene transcription and protein production in CD4+ Jurkat T cells. Strikingly, we show that this repression is due to a tryptophan at residue 32 of Tat E and is secondary to interference with recruitment of the histone acetyltransferase P/CAF to the TNF promoter and with chromatin remodeling of the TNF locus. This study presents a novel mechanism by which HIV-1 manipulates a host immune response gene that is important in its own replication. Moreover, these results demonstrate a new mechanism by which the TNF gene is regulated via chromatin remodeling secondary to viral infection.

Original languageEnglish (US)
Pages (from-to)4182-4190
Number of pages9
JournalJournal of Immunology
Volume176
Issue number7
StatePublished - Apr 1 2006
Externally publishedYes

Fingerprint

Chromatin Assembly and Disassembly
Trans-Activators
HIV-1
Gene Expression
Genes
Histone Acetyltransferases
Proteins
Jurkat Cells
Virus Diseases
Tryptophan
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

@article{522b044e89d74e1299ef14165c9e8350,
title = "Transactivator of transcription from HIV type 1 subtype E selectively inhibits TNF gene expression via interference with chromatin remodeling of the TNF locus",
abstract = "The transactivator of transcription (Tat) protein is essential for efficient HIV type 1 (HIV-1) replication and is involved in the transcriptional regulation of the host immune response gene, TNF. In this study, we demonstrate that Tat proteins from representative HIV-1 subtype E isolates, but not from subtypes B or C, selectively inhibit TNF gene transcription and protein production in CD4+ Jurkat T cells. Strikingly, we show that this repression is due to a tryptophan at residue 32 of Tat E and is secondary to interference with recruitment of the histone acetyltransferase P/CAF to the TNF promoter and with chromatin remodeling of the TNF locus. This study presents a novel mechanism by which HIV-1 manipulates a host immune response gene that is important in its own replication. Moreover, these results demonstrate a new mechanism by which the TNF gene is regulated via chromatin remodeling secondary to viral infection.",
author = "Shahin Ranjbar and {Rajsbaum Gorodezky}, Ricardo and Goldfeld, {Anne E.}",
year = "2006",
month = "4",
day = "1",
language = "English (US)",
volume = "176",
pages = "4182--4190",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

TY - JOUR

T1 - Transactivator of transcription from HIV type 1 subtype E selectively inhibits TNF gene expression via interference with chromatin remodeling of the TNF locus

AU - Ranjbar, Shahin

AU - Rajsbaum Gorodezky, Ricardo

AU - Goldfeld, Anne E.

PY - 2006/4/1

Y1 - 2006/4/1

N2 - The transactivator of transcription (Tat) protein is essential for efficient HIV type 1 (HIV-1) replication and is involved in the transcriptional regulation of the host immune response gene, TNF. In this study, we demonstrate that Tat proteins from representative HIV-1 subtype E isolates, but not from subtypes B or C, selectively inhibit TNF gene transcription and protein production in CD4+ Jurkat T cells. Strikingly, we show that this repression is due to a tryptophan at residue 32 of Tat E and is secondary to interference with recruitment of the histone acetyltransferase P/CAF to the TNF promoter and with chromatin remodeling of the TNF locus. This study presents a novel mechanism by which HIV-1 manipulates a host immune response gene that is important in its own replication. Moreover, these results demonstrate a new mechanism by which the TNF gene is regulated via chromatin remodeling secondary to viral infection.

AB - The transactivator of transcription (Tat) protein is essential for efficient HIV type 1 (HIV-1) replication and is involved in the transcriptional regulation of the host immune response gene, TNF. In this study, we demonstrate that Tat proteins from representative HIV-1 subtype E isolates, but not from subtypes B or C, selectively inhibit TNF gene transcription and protein production in CD4+ Jurkat T cells. Strikingly, we show that this repression is due to a tryptophan at residue 32 of Tat E and is secondary to interference with recruitment of the histone acetyltransferase P/CAF to the TNF promoter and with chromatin remodeling of the TNF locus. This study presents a novel mechanism by which HIV-1 manipulates a host immune response gene that is important in its own replication. Moreover, these results demonstrate a new mechanism by which the TNF gene is regulated via chromatin remodeling secondary to viral infection.

UR - http://www.scopus.com/inward/record.url?scp=33646069367&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646069367&partnerID=8YFLogxK

M3 - Article

VL - 176

SP - 4182

EP - 4190

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -