Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus

DOI Web Site 被引用文献41件
  • Leonid Gitlin
    *Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, 660 South Euclid Avenue, St. Louis, MO 63110;
  • Winfried Barchet
    *Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, 660 South Euclid Avenue, St. Louis, MO 63110;
  • Susan Gilfillan
    *Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, 660 South Euclid Avenue, St. Louis, MO 63110;
  • Marina Cella
    *Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, 660 South Euclid Avenue, St. Louis, MO 63110;
  • Bruce Beutler
    Department of Immunology, Scripps Research Institute, La Jolla, CA 92037; and
  • Richard A. Flavell
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520
  • Michael S. Diamond
    Division of Infectious Diseases, Department of Medicine, and
  • Marco Colonna
    *Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, 660 South Euclid Avenue, St. Louis, MO 63110;

書誌事項

公開日
2006-05-30
DOI
  • 10.1073/pnas.0603082103
公開者
Proceedings of the National Academy of Sciences

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説明

<jats:p> 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 (polyI:C), the synthetic analog of viral dsRNA, and mediate type I IFN responses to polyI:C and multiple RNA viruses <jats:italic>in vitro</jats:italic> . We generated mda-5-deficient mice and showed that mda-5 is the dominant receptor mediating type I IFN secretion in response to polyI:C <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic> . Moreover, mda-5−/− mice exhibited a selectively impaired antiviral response to encephalomyocarditis picornavirus, indicating functional specialization of mda-5 <jats:italic>in vivo</jats:italic> . </jats:p>

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