PEDV nonstructural protein 14 inhibits RIPK3 and RIPK1-mediated PANoptosis.

Abstract

Porcine epidemic diarrhea virus (PEDV) is one of the primary pathogens responsible for severe diarrhea in piglets, causing significant economic losses to the global swine industry. PANoptosis is a critical strategy for the host to resist viral invasion, but the mechanism by which PEDV evades the PANoptosis response remains unclear. In this study, we found that PANoptosis agonists significantly reduce PEDV replication and that PEDV Nsp14 specifically inhibits the activation of the ZBP1-RIPK3-MLKL axis. Mechanistically, we observed that Nsp14 inhibits the promoter activity of RIPK3 and RIPK1, thereby suppressing signal transduction. Additionally, RIPK1 can also recruit Caspase 8 to degrade Nsp14, thereby blocking PEDV replication. Our study reveals the function and mechanism of Nsp14 in PEDV-induced PANoptosis, providing new insights into how PEDV infection and immune evasion.