Abstract
Pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs) and RIG-like helicase (RLH) receptors, are involved in innate immune antiviral responses. Here we show that nucleotide-binding oligomerization domain 2 (Nod2) can also function as a cytoplasmic viral PRR by triggering activation of interferon-regulatory factor 3 (IRF3) and production of interferon-beta (IFN-beta). After recognition of a viral ssRNA genome, Nod2 used the adaptor protein MAVS to activate IRF3. Nod2-deficient mice failed to produce interferon efficiently and showed enhanced susceptibility to virus-induced pathogenesis. Thus, the function of Nod2 as a viral PRR highlights the important function of Nod2 in host antiviral defense mechanisms.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / immunology
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Cell Line
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Enzyme-Linked Immunosorbent Assay
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Fluorescent Antibody Technique
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Humans
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Immune System Phenomena
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Immunity, Innate*
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Immunoblotting
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Immunoprecipitation
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In Situ Nick-End Labeling
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Interferon Regulatory Factor-3 / biosynthesis
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Interferon Regulatory Factor-3 / immunology
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Interferon-beta / biosynthesis
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Interferon-beta / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Nod2 Signaling Adaptor Protein / genetics
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Nod2 Signaling Adaptor Protein / immunology*
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Nod2 Signaling Adaptor Protein / metabolism
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RNA, Small Interfering
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RNA, Viral / immunology*
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Receptors, Pattern Recognition / genetics
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Receptors, Pattern Recognition / immunology
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Receptors, Pattern Recognition / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Adaptor Proteins, Signal Transducing
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IRF3 protein, human
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Interferon Regulatory Factor-3
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MAVS protein, human
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NOD2 protein, human
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Nod2 Signaling Adaptor Protein
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RNA, Small Interfering
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RNA, Viral
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Receptors, Pattern Recognition
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Interferon-beta