Viruses Seen by Our Cells: The Role of Viral RNA Sensors

Figure 2

The pathways induced by RIG-I. Activation of RIG-I is regulated by many posttranslational modifications such as phosphorylation and ubiquitination. In resting cells, inactive RIG-I is kept in a close conformation by PKCα. PKCβ and CK2 phosphorylate both CARDs and CTD. Upon viral infection, PP1α and PP1β dephosphorylate RIG-I to allow the binding of viral RNA within its ATPase-helicase domain which shifts RIG-I to an open conformation and allows the CTD to be ubiquitinated by Riplet. Once activated, TRIM25 allows for the recruitment of K63-polyubiquitin chains via TRIM25 which allow RIG-I dimerization and recruitment to the adaptor protein MAVS. To balance immune activation, CYLD, UPS1, UPS3, RNF122, and RNF125 actively antagonize RIG-I activation by the degradation of K63-polyubiquitin chains and a switch to K48-polyubiquitin chains that tag RIG-I for proteasome degradation. This interaction allows for the oligomerization of MAVS and the recruitment of regulatory subunits TRAF2, TRAF5, TRAF6, and NEMO. This signaling culminates with the phosphorylation of immune transcription factors via IKBKE, TBK1, and IKK protein kinases, leading to their nuclear translocation and production of type 1 IFN with subsequent expression of ISGs.