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

370 Scopus citations

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 (US)
Pages (from-to)5532-5539
Number of pages8
JournalJournal of virology
Volume76
Issue number11
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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