Essential role of mda-5 in type I IFN responses to polyriboinosinic

polyribocytidylic acid and encephalomyocarditis picornavirus

Leonid Gitlin, Winfried Barchet, Susan Gilfillan, Marina Cella, Bruce Beutler, Richard A. Flavell, Michael S. Diamond, Marco Colonna

Research output: Contribution to journalArticle

777 Citations (Scopus)

Abstract

The innate immune system recognizes viral dsRNA through two distinct pathways; the Toll-like receptor 3 (TLR3) pathway detects dsRNA phagocytosed in endosomes; the helicases retinoic acid-induced protein I (RIG-I) and melanoma differentiation-associated gene-5 (mda-5) detect cytoplasmic dsRNA generated during viral replication. Both RIG-I and mda-5 can bind polyriboinosinic: polyribocytidylic acid (polyl:C), the synthetic analog of viral dsRNA, and mediate type I IFN responses to polyl:C and multiple RNA viruses in vitro. We generated mda-5-deficient mice and showed that mda-5 is the dominant receptor mediating type I IFN secretion in response to polyl:C in vitro and in vivo. Moreover, mda-5-/- mice exhibited a selectively impaired antiviral response to encephalomyocarditis picornavirus, indicating functional specialization of mda-5 in vivo.

Original languageEnglish (US)
Pages (from-to)8459-8464
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number22
DOIs
StatePublished - May 30 2006

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Picornaviridae
Melanoma
Genes
Toll-Like Receptor 3
Acids
Endosomes
RNA Viruses
Tretinoin
Phagocytosis
Antiviral Agents
polyriboinosinic-polyribocytidylic acid
Immune System

Keywords

  • Innate immunity
  • Virus

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Essential role of mda-5 in type I IFN responses to polyriboinosinic : polyribocytidylic acid and encephalomyocarditis picornavirus. / Gitlin, Leonid; Barchet, Winfried; Gilfillan, Susan; Cella, Marina; Beutler, Bruce; Flavell, Richard A.; Diamond, Michael S.; Colonna, Marco.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 22, 30.05.2006, p. 8459-8464.

Research output: Contribution to journalArticle

Gitlin, Leonid ; Barchet, Winfried ; Gilfillan, Susan ; Cella, Marina ; Beutler, Bruce ; Flavell, Richard A. ; Diamond, Michael S. ; Colonna, Marco. / Essential role of mda-5 in type I IFN responses to polyriboinosinic : polyribocytidylic acid and encephalomyocarditis picornavirus. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 22. pp. 8459-8464.
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