Activation of innate immune antiviral responses by Nod2

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). Following recognition of viral ssRNA genome, NOD2 utilized the adaptor protein MAVS (mitochondrial antiviral signaling) to activate IRF3. NOD2-deficient mice failed to produce IFN efficiently and exhibited enhanced susceptibility to virus-induced pathogenesis. Thus, the function of NOD2 as a viral PRR highlights the important role of NOD2 in host antiviral defense mechanisms.

Cloning of two rainbow trout nucleotide-binding oligomerization domain containing 2 (NOD2) splice variants and functional characterization of the NOD2 effector domains

“…However, recent work has shown that human NOD2 can also activate IRF3 and interferon in RSV-infected cells, which highlights an important function of NOD2 in host antiviral defences [14]. In the present study, one interesting finding was the ability of the trout NOD2 effector domains to affect not only type I interferon expression but also type II interferon expression.…”

“…NOD2 signaling by activating NF-kB and MAPKs leads to the induction of proinflammatory cytokines and chemokines [12], and anti-microbial peptides [13], which mediate the antimicrobial response. Besides the function in antibacterial defence, new studies show that NOD2 also has an important role in recognizing viruses and inducing type I IFN production through association with the mitochondrial antiviral signaling protein (MAVS) [14].…”

Evading innate immunity in nonviral mRNA delivery: don’t shoot the messenger

“…This complex, called "the inflammasome", is responsible for the proteolytic maturation of the IL-1β and IL-18 cytokines. A recent study by Sabbah et al has demonstrated that another member of the NLRs, NOD2, can also serve to detect ssRNA [52].…”

Muramyl dipeptide responsive pathways in Crohn’s disease: from NOD2 and beyond

“…Sabbah et al [131] reported that NOD2 is involved in induction of antiviral cytokines, including IFN-β, in response to external viral stimuli such as single-stranded RNA (ssRNA) and respiratory syncytial virus (RSV). The authors found that the activation mechanism requires NBD and LRR domain of NOD2 interaction with the mitochondrial antiviral signaling (MAVS) protein.…”