Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5

Brisse, Morgan; Ly, Hinh

Finally, TRIM25 has been found to be essential for RIG-I activation and IFN signaling in-vitro and in-vivo. For the former, siRNA-mediated knock-down (110, 111) , cellular knockout (112) and inhibition by viral protein (109, (113) (114) (115) (116) conditions for TRIM25 in multiple cell types have been shown to change RIG-I cellular localization (110) and to negatively affect RIG-I K63 ubiquitination, association with MAVS and IFN signaling [when the constitutively active RIG-I CARD domain was overexpressed (109, (112) (113) (114) (115) (116) or during viral infection (109, 111, 114) ]. Viral inhibition of TRIM25 may even be a source of a positive selection during the evolution of certain viruses, as NS1 IAV proteins have been found to interact with species specific TRIM25 (114) . For the latter, MEFs from TRIM25 KO mice have significantly downregulated IFN1 production upon viral infection (113) and KO mice for NLRP12, which is a competitive interactor with TRIM25 to RIG-I, show increased interferon production and more resistance to viral infection (117) . The known contributions of TRIM25 to innate immunity have recently been summarized elsewhere (52) .