Activation of innate immune antiviral response by NOD2

Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Nature Immunology (Impact Factor: 20). 09/2009; 10(10):1073-80. DOI: 10.1038/ni.1782
Source: PubMed


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.

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Available from: Kaoru Tominaga, Oct 04, 2015
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    • "NOD1 and NOD2 detect bacterial peptidoglycan-derived molecules, meso-diaminopimelic acid (DAP) and muramyl dipeptide (MDP), respectively (Kanneganti et al., 2007). In addition, NOD2 also functions as a viral PRR, being important for the production of type I IFNs in response to ssRNA virus (Sabbah et al., 2009). IPAF and NAIP detect intracellular flagellin, leading to inflammasome activation through a TLR5-independent pathway (Franchi et al., 2006; Miao et al., 2006; Ren et al., 2006). "
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    ABSTRACT: Lower vertebrates have been found to possess over 200 NACHT-domain encoding genes; but, to date, very little is known about their functional activity. This article describes the sequences and expression analysis of two zebrafish NACHT-containing proteins, namely NALPL1 and NALPL2. In addition, the functions of zebrafish NALPL1 and NALPL2, which are absent for both amino-terminal effector-binding domain (EBD) and carboxy-terminal ligand-recognition domain (LRD), were investigated for the first time in fish species. The predicted NALPL1 and NALPL2 proteins consist of 651 and 847 amino acids (aa), respectively, with both molecules only containing NACHT domain, which were different from other NACHT-family members. Phylogenetic analysis showed that zebrafish NALPL1 and NALPL2 have a closer relationship with mammalian NALP subfamily than NOD subfamily. The differential expression patterns of NALPL1 and NALPL2 in development stages and organs were observed, suggesting the difference of action phase and effector organ of NALPL1 and NALPL2. When the modulation of NALPL1 and NALPL2 in pathogen infection was analyzed, it was found that the two molecules were upregulated by both bacterial and viral infection. Overexpression of NALPL1 and NALPL2 resulted in significant inhibition for intracellular Edwardsiella tarda growth. Further studies demonstrated that NALPL1 and NALPL2 also contributed to protection against viral infection. These results demonstrate that both NALPL1 and NALPL2 are important intracellular proteins in host surveillance against both bacterial and viral infection. Interestingly, the expression of downstream signaling genes was not affected by the overexpression of NALPL1 or NALPL2, but NOD1 and MDA5 were upregulated by NALPL1 or NALPL2 overexpression, suggesting that they likely act in pathogen infection through the interaction with other PRRs.
    Developmental & Comparative Immunology 10/2014; 46(2):323–332. DOI:10.1016/j.dci.2014.05.007 · 2.82 Impact Factor
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    • "The high antigenic drift rate observed in the influenza virus is one of primary reasons why constantly updated seasonal influenza vaccination is recommended. Genomic variability of the influenza virus has been largely investigated over the years, yet the variability of the host remains a sparsely documented topic, despite its crucial impact on the immune response (Wijburg et al., 1997; Matrosovich & Klenk, 2003; Schmitz et al., 2005; Jayasekera et al., 2007; Koyama et al., 2007; Throsby et al. 2008; Ichinohe et al., 2009; Sabbah et al., 2009; Kreijtz et al., 2011; Zhou et al., 2012; Henn et al., 2013; Hertz et al., 2013; Lin & Brass, 2013) and the course of infection. The goal of this review is to explore genomic variability in the host genes that mediate host-pathogen interactions. "
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    ABSTRACT: The aftermath of influenza infection is determined by a complex set of host-pathogen interactions, where genomic variability on both viral and host sides influences the final outcome. Although there exists large body of literature describing influenza virus variability, only a very small fraction covers the issue of host variance. The goal of this review is to explore the variability of host genes responsible for host-pathogen interactions, paying particular attention to genes responsible for the presence of sialylated glycans in the host endothelial membrane, mucus, genes used by viral immune escape mechanisms, and genes particularly expressed after vaccination, since they are more likely to have a direct influence on the infection outcome.
    Acta biochimica Polonica 09/2014; 61:403-419. · 1.15 Impact Factor
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    • "Consequent activation of the key downstream signaling molecules NF-κB and MAP kinase ultimately results in production of inflammatory cytokines such as IL-1β, IL-6, IL-8, TNF-α, and a variety of other cytokines, chemokines and adhesion molecules. The physiological role of NOD2 has been expanding beyond being an innate line of defense against intracellular bacterial infections and equally involves a role in the defense against Toxoplasma[46], as a viral pattern recognition receptor [47], and in the induction of the autophagy process initiated by intracellular bacteria eg Shigella flexneri[48]. "
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    ABSTRACT: Blau syndrome is a monogenic disease resulting from mutations in the pattern recognition receptor NOD2, and is phenotypically characterized by the triad of granulomatous polyarthritis, dermatitis and uveitis. This paper reviews briefly the classical clinical features of the disease, as well as more recently described extra-triad symptoms. From an ongoing prospective multicenter study, we provide new data on the natural history of Blau syndrome, focusing on functional status and visual outcome. We also present an update of the range of different NOD2 mutations found in Blau syndrome as well as recent data on morphologic and immunohistochemical characteristics of the Blau granuloma. Finally, emerging insights into pathogenic mechanisms including activation of NOD2 signal transduction, and potential biomarkers of disease activity are discussed.
    Pediatric Rheumatology 08/2014; 12(1):33. DOI:10.1186/1546-0096-12-33 · 1.61 Impact Factor
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