Fig. 8

Schematic illustration of TRIM18 serving as a negative regulator in antiviral innate immunity against organ inflammations induced by RNA and DNA viruses. In WT macrophages after infections with DNA and RNA viruses, TRIM18 interacts with PPM1A and induces its K63-linked ubiquitination for maintaining stability of PPM1A, thereby further dephosphorylating TBK1 for its inactivation and blocking the interactions of TBK1 with its upstream adaptors STING and MAVS leading to dramatic reduction of type I IFN, which promotes viral myocarditis and more massive inflammations in lung and brain. In contrast, in TRIM18 KO macrophages post infections with DNA and RNA viruses, PPM1A could not maintain its stability without TRIM18, and loss its strong ability to inactivate TBK1 resulting in significant induction of type I IFN, which restricts viral myocarditis, inflammations in lung and brain