Abstract
Toll-like receptors (TLRs) play an important role in antiviral response by recognizing viral components. Recently, a RNA helicase, RIG-I, was also suggested to recognize viral double-stranded RNA. However, how these molecules contribute to viral recognition in vivo is poorly understood. We show by gene targeting that RIG-I is essential for induction of type I interferons (IFNs) after infection with RNA viruses in fibroblasts and conventional dendritic cells (DCs). RIG-I induces type I IFNs by activating IRF3 via IkappaB kinase-related kinases. In contrast, plasmacytoid DCs, which produce large amounts of IFN-alpha, use the TLR system rather than RIG-I for viral detection. Taken together, RIG-I and the TLR system exert antiviral responses in a cell type-specific manner.
MeSH terms
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Animals
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DEAD Box Protein 58
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DEAD-box RNA Helicases
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DNA-Binding Proteins / metabolism
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dendritic Cells / virology
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Fibroblasts / immunology*
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Fibroblasts / metabolism
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Fibroblasts / virology
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Gene Targeting
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I-kappa B Kinase
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Interferon Regulatory Factor-3
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Interferon Type I / metabolism
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Interferon-alpha / metabolism
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Newcastle Disease / enzymology
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Newcastle Disease / immunology
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Newcastle disease virus / immunology
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Protein Serine-Threonine Kinases / metabolism
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RNA Helicases / genetics
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RNA Helicases / physiology*
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RNA Virus Infections / enzymology*
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RNA Virus Infections / immunology*
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / physiology*
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Signal Transduction
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Toll-Like Receptors
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Transcription Factors / metabolism
Substances
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DNA-Binding Proteins
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Interferon Regulatory Factor-3
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Interferon Type I
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Interferon-alpha
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Irf3 protein, mouse
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Membrane Glycoproteins
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Receptors, Cell Surface
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Toll-Like Receptors
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Transcription Factors
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Protein Serine-Threonine Kinases
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Chuk protein, mouse
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I-kappa B Kinase
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Ikbkb protein, mouse
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Ikbke protein, mouse
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Ddx58 protein, mouse
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DEAD Box Protein 58
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DEAD-box RNA Helicases
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RNA Helicases