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

815 Scopus citations

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
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

Keywords

  • Innate immunity
  • Virus

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