Activation of Innate Immune Antiviral Responses by Nod2

Nat Immunol. 2009 Oct;10(10):1073-80. doi: 10.1038/ni.1782. Epub 2009 Aug 23.

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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cell Line
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Humans
  • Immune System Phenomena
  • Immunity, Innate*
  • Immunoblotting
  • Immunoprecipitation
  • In Situ Nick-End Labeling
  • Interferon Regulatory Factor-3 / biosynthesis
  • Interferon Regulatory Factor-3 / immunology
  • Interferon-beta / biosynthesis
  • Interferon-beta / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Nod2 Signaling Adaptor Protein / genetics
  • Nod2 Signaling Adaptor Protein / immunology*
  • Nod2 Signaling Adaptor Protein / metabolism
  • RNA, Small Interfering
  • RNA, Viral / immunology*
  • Receptors, Pattern Recognition / genetics
  • Receptors, Pattern Recognition / immunology
  • Receptors, Pattern Recognition / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Adaptor Proteins, Signal Transducing
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • RNA, Small Interfering
  • RNA, Viral
  • Receptors, Pattern Recognition
  • VISA protein, human
  • Interferon-beta