Fig. 1.

NOD2 signaling bifurcates into antibacterial and antiviral effector arms. A model of NOD2 signaling is presented in which NOD2 is bound to the chaperonin and ubiquitin ligase pair, HSP90 and SGT in the basal state (Complex A). This is thought to hold the inactive NOD2 in a signaling competent form (48). Upon stimulation with MDP, NOD2 binds to RIP2, and activates NF-κB and MAPK (p38 and JNK) through recruitment of several intracellular proteins, including cIAP1 and cIAP2 (Complex B). This leads to in the induction of chemokines, cytokines and defensins, which mediate the antimicrobial responses. Similarly, viral infection can activate NOD2, leading to its translocation to the mitochondria, association with MAVS, and the induction of the antiviral cytokine, type I interferon (Complex C). Double stranded RNA, and possibly single stranded RNA, induces OAS-2 to interact with NOD2. NOD2 then stimulates the production of -5’ oligoadenylate synthase type 2, which activates antiviral responses including RNaseL activation (Complex C). RIG-I is depicted because it is the PRR that binds to viral nucleic acids, while TBK and IKK-e lies downstream of MAVS to activate IRF-3.