Cytoplasmic Pattern Receptors (RIG-I and MDA-5) and Signaling in Viral Infections

This chapter focuses on the roles of retinoic acid-inducible gene I (RIG-I)-like RNA helicases (RLHs) in RNA virus recognition and RLH signaling pathways. It describes the roles of the toll-like receptors (TLRs) system with respect to the relationship between these two virus recognition mechanisms during the course of RNA virus infections in vivo. RIG-I mediated signaling is positively and negatively controlled by ubiquitination of RIG-I. First, the caspase recruitment domains (CARDs) of RIG-I undergo Lys-63-linked ubiquitination by tripartite motif (TRIM) 25, a ubiquitin E3 ligase composed of a RING finger domain, B box/coiled-coil domain, and SPRY domain. In addition to RLHs, TLRs are also important in recognizing virus infections. Innate immediate immune responses are important for mounting acquired immune responses to viral infections. Recently, two different virus infection models have been analyzed to examine the roles of RLHs and TLRs in the activation of acquired immune responses. The contributions of these two melanoma differentiation-associated gene 5 (MDA-5) and TLR3 systems to the activation of T-cell responses have been examined. Recent progress in studies of RLHs and their signaling pathways has revealed that the RLH system is essential for inducing innate immune responses in response to RNA viruses infecting cells. Furthermore, various immune cells cooperate in order to establish optimized antiviral immune responses. Thus, studies monitoring immune responses in vivo could be vital to fully clarify the mechanisms of antiviral immune responses.