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 (polyI:C), the synthetic analog of viral dsRNA, and mediate type I IFN responses to polyI: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 polyI: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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Bone Marrow Cells / cytology
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Cardiovirus Infections / genetics
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Cardiovirus Infections / immunology*
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Cardiovirus Infections / pathology
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Cardiovirus Infections / virology
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Cell Differentiation
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Cells, Cultured
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DEAD-box RNA Helicases
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Dendritic Cells / cytology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Disease Susceptibility
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Encephalomyocarditis virus / immunology*
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Interferon Type I / immunology*
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Interferon Type I / metabolism
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Interferon-Induced Helicase, IFIH1
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Macrophages / drug effects
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Macrophages / metabolism
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Mice
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Mice, Knockout
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Polynucleotides / immunology*
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RNA Helicases / deficiency
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RNA Helicases / genetics
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RNA Helicases / metabolism*
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Survival Rate
Substances
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Interferon Type I
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Polynucleotides
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poly(rI).poly(dC)
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Ifih1 protein, mouse
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DEAD-box RNA Helicases
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Interferon-Induced Helicase, IFIH1
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RNA Helicases