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Nature Immunology 10, 1073–1080 (1 October 2009) | doi:10.1038/ni.1782

Activation of innate immune antiviral responses by Nod2

Ahmed Sabbah , Te Hung Chang , Rosalinda Harnack , Victoria Frohlich , Kaoru Tominaga , Peter H Dube , Yan Xiang & Santanu Bose

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-β (IFN-β). 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.