Activation of innate immune antiviral responses by Nod2.
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.
Sabbah
Ahmed
A
Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Chang
Te Hung
TH
Harnack
Rosalinda
R
Frohlich
Victoria
V
Tominaga
Kaoru
K
Dube
Peter H
PH
Xiang
Yan
Y
Bose
Santanu
S
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D055633:Immune System Phenomena; D007113:Immunity, Innate; D015151:Immunoblotting; D047468:Immunoprecipitation; D020287:In Situ Nick-End Labeling; D050838:Interferon Regulatory Factor-3 / Q000096:biosynthesis / Q000276:immunology; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D034741:RNA, Small Interfering; D012367:RNA, Viral / Q000276:immunology*; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C505371:MAVS protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D034741:RNA, Small Interfering; D012367:RNA, Viral; D051192:Receptors, Pattern Recognition; D016899:Interferon-beta
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