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Activation of innate immune antiviral responses by Nod2

Nature Immunology volume 10, pages 1073–1080 (2009)Cite this article

A Corrigendum to this article was published on 01 October 2010

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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-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.

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Figure 1: Activation of Nod2 by ssRNA.
Figure 2: Activation of antiviral response by Nod2 in virus infected cells.
Figure 3: Nod2 is required for interferon production.
Figure 4: Activation of Nod2 by viral ssRNA.
Figure 5: Function of MAVS during Nod2-mediated activation of the antiviral pathway.
Figure 6: Interaction of MAVS with Nod2.
Figure 7: The NBD and LRR domains of Nod2 are essential for interaction with MAVS.
Figure 8: Nod2 is essential for host defense against viral infection.

Change history

  • 25 June 2010

    In the version of this article initially published, some panels in Figure 8e were incorrect. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank K. Li (University of Tennessee Health Science Center) for reagents; A. Garcia-Sastre (Mount Sinai School of Medicine) for influenza A virus; Z.J. Chen (University of Texas Southwestern Medical Center) for MAVS-deficient MEFs; the Core Optical Imaging Facility (University of Texas Health Science Center at San Antonio) for confocal images; and K. Moncada Gorena and C. Thomas in the Flow Cytometry Core Facility (supported by the National Institutes of Health (P30 CA54174 to the San Antonio Cancer Institute; P30 AG013319 to the Nathan Shock Center; and P01AG19316)) for flow cytometry. Supported by National Institutes of Health (AI069062 to S.B., CA129246 to S.B. and T32-DE14318 to A.S. and AI067716 to P.H.D.) and the American Lung Association (RG-49629-N to S.B. and AI067716 to P.H.D.).

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  1. Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

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

  2. Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

    Victoria Frohlich & Kaoru Tominaga

  3. Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

    Kaoru Tominaga

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Contributions

A.S. and S.B. designed the experiments and prepared the manuscript; A.S. and T.H.C. did the experiments; R.H. provided technical assistance and did several experiments; Y.X. did the experiments with vaccinia virus; V.F. did the immunofluorescence analysis; K.T. did the studies with mouse embryo fibroblasts; and P.H.D. did the MPO assay.

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Correspondence to Santanu Bose.

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Sabbah, A., Chang, T., Harnack, R. et al. Activation of innate immune antiviral responses by Nod2. Nat Immunol 10, 1073–1080 (2009). https://doi.org/10.1038/ni.1782

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