Transcriptional profiling of interferon regulatory factor 3 target genes: Direct involvement in the regulation of interferon-stimulated genes

Nathalie Grandvaux, Marc J. Servant, Benjamin TenOever, Ganes C. Sen, Siddarth Balachandran, Glen N Barber, Rongtuan Lin, John Hiscott

Research output: Contribution to journalArticle

361 Citations (Scopus)

Abstract

Ubiquitously expressed interferon regulatory factor 3 (IRF-3) is directly activated after virus infection and functions as a key activator of the immediate-early alpha/beta interferon (IFN) genes, as well as the RANTES chemokine gene. In the present study, a tetracycline-inducible expression system expressing a constitutively active form of IRF-3 (IRF-3 5D) was combined with DNA microarray analysis to identify target genes regulated by IRF-3. Changes in mRNA expression profiles of 8,556 genes were monitored after Tet-inducible expression of IRF-3 5D. Among the genes upregulated by IRF-3 were transcripts for several known IFN-stimulated genes (ISGs). Subsequent analysis revealed that IRF-3 directly induced the expression of ISG56 in an IFN-independent manner through the IFN-stimulated responsive elements (ISREs) of the ISG56 promoter. These results demonstrate that, in addition to its role in the formation of a functional immediate-early IFN-β enhanceosome, IRF-3 is able to discriminate among ISRE-containing genes involved in the establishment of the antiviral state as a direct response to virus infection.

Original languageEnglish
Pages (from-to)5532-5539
Number of pages8
JournalJournal of Virology
Volume76
Issue number11
DOIs
StatePublished - May 27 2002
Externally publishedYes

Fingerprint

Interferon Regulatory Factor-3
interferons
Interferons
Genes
genes
Virus Diseases
interferon-beta
Chemokine CCL5
viruses
interferon regulatory factor-3
Interferon-beta
chemokines
Microarray Analysis
Tetracycline
Oligonucleotide Array Sequence Analysis
tetracycline
Chemokines
Interferon-alpha
infection
Antiviral Agents

ASJC Scopus subject areas

  • Immunology

Cite this

Transcriptional profiling of interferon regulatory factor 3 target genes : Direct involvement in the regulation of interferon-stimulated genes. / Grandvaux, Nathalie; Servant, Marc J.; TenOever, Benjamin; Sen, Ganes C.; Balachandran, Siddarth; Barber, Glen N; Lin, Rongtuan; Hiscott, John.

In: Journal of Virology, Vol. 76, No. 11, 27.05.2002, p. 5532-5539.

Research output: Contribution to journalArticle

Grandvaux, Nathalie ; Servant, Marc J. ; TenOever, Benjamin ; Sen, Ganes C. ; Balachandran, Siddarth ; Barber, Glen N ; Lin, Rongtuan ; Hiscott, John. / Transcriptional profiling of interferon regulatory factor 3 target genes : Direct involvement in the regulation of interferon-stimulated genes. In: Journal of Virology. 2002 ; Vol. 76, No. 11. pp. 5532-5539.
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