TRIM25 potentiates innate immune response to Senecavirus A by enhancing K63-linked ubiquitination of RIG-I and K48-linked ubiquitin-facilitated degradation of PFKP

Abstract

The in-depth understand of interaction between Senecavirus A (SVA) and the host is of great significance to control viral prevalence. Here, tripartite motif 25 (TRIM25) potentiates innate immune response to SVA by enhancing K48-linked ubiquitin-facilitated degradation of platelet type phosphofructokinase (PFKP) and K63-linked ubiquitination of retinoic acid-inducible gene-I (RIG-I) was reported. Infection experiments results showed TRIM25 enhanced the K63-linked ubiquitination of RIG-I to activate innate immune response to SVA. TRIM25 inhibits SVA-induced glycolysis by enhancing K48-linked ubiquitin-facilitated degradation of PFKP, which is confirmed to inhibit the RIG-I signal pathway by increasing glycolysis. And TRIM25 induced degradation of PFKP is associated with 26S proteasome. Furthermore, SVA inhibits the K63-linked ubiquitination of RIG-I by destabilizing the interaction between TRIM25 and RIG-I, and decreases the K48-linked ubiquitination of PFKP mediated by TRIM25. These results provide new data on interaction between SVA and the host, and depict a novel pathway for SVA to achieve immune escape based on TRIM25.