Fas-associated death domain-containing protein-mediated antiviral innate immune signaling involves the regulation of Irf7

Siddharth Balachandran, Thiagarajan Venkataraman, Paul B. Fisher, Glen N Barber

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The induction of type I (αβ) IFN following virus infection is necessary tor the stimulation of effective antiviral host defense. In fibroblasts, a subset of primary genes (including those encoding IFN-β and IFN-α4) are induced directly by intracellular dsRNA generated by the virus during its replication. These primary type I IFNs induce expression of IFN regulatory factor (IRF)-7, required for production of a second cascade of IFN-α subtypes and the further establishment of a complete antiviral state. Previously, we had reported on a role for Fas-associated death domain-containing protein (FADD) in the control of TLR-independent innate immune responses to virus infection. Our data in this study demonstrate that FADD is not only required for efficient primary gene induction, but is also essential for induction of Irf7 and effective expression of secondary IFN-αs and other antiviral genes. Ectopic overespression of IRF-7 partially rescued dsRNA responsiveness and IFN-α production, and a constitutively active variant of IRF-7 displayed normal activity in Fadd-/- murine embryonic fibroblasts. MC159, a FADD-interacting viral protein encoded by the molluscum contagiosum poxvirus was found to inhibit dsRNA-activated signaling events upstream of IRF-7. These data indicate that FADD's antiviral activity involves regulation of IRF-7-dependent production of IFN-α subtypes and consequent induction of secondary antiviral genes.

Original languageEnglish
Pages (from-to)2429-2439
Number of pages11
JournalJournal of Immunology
Volume178
Issue number4
StatePublished - Feb 15 2007

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Fas-Associated Death Domain Protein
Antiviral Agents
Virus Diseases
Genes
Fibroblasts
Molluscum Contagiosum
Poxviridae
Viral Proteins
Innate Immunity
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

Fas-associated death domain-containing protein-mediated antiviral innate immune signaling involves the regulation of Irf7. / Balachandran, Siddharth; Venkataraman, Thiagarajan; Fisher, Paul B.; Barber, Glen N.

In: Journal of Immunology, Vol. 178, No. 4, 15.02.2007, p. 2429-2439.

Research output: Contribution to journalArticle

Balachandran, Siddharth ; Venkataraman, Thiagarajan ; Fisher, Paul B. ; Barber, Glen N. / Fas-associated death domain-containing protein-mediated antiviral innate immune signaling involves the regulation of Irf7. In: Journal of Immunology. 2007 ; Vol. 178, No. 4. pp. 2429-2439.
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