Porcine epidemic diarrhea virus 3CLpro causes apoptosis and collapse of mitochondrial membrane potential requiring its protease activity and signaling through MAVS.

Porcine epidemic diarrhea (PED) is a highly contagious and virulent intestinal infectious disease characterized by diarrhea, vomiting and dehydration. Although PEDV-induced apoptosis has been characterized in vitro and vivo, the functional proteins related to this event and the mechanism still need further research. Here, we firstly demonstrated that PEDV epidemic strain JS2013 could trigger apoptosis in a dose- and time-dependent manner. Then, PEDV 3CLpro was further identified as a crucial inducer of PEDV-triggered apoptosis. In addition, using site-directed mutagenesis to disrupt the protease activity of 3CLpro by His41 and Cys144 mutations, we found that 3CLpro-induced apoptosis and mitochondrial damage significantly reduced, suggesting that the protease activity of 3CLpro was essential for apoptosis and mitochondrial damage. Furthermore, PEDV 3CLpro could synergistically promote MAVS-mediated apoptosis and MAVS was involved in the signaling pathway of 3CLpro-induced apoptosis, but no direct interaction between PEDV 3CLpro and MAVS was detected by immunoprecipitation assays. Our findings provide important insights into the role of 3CLpro in the pathogenicity of PEDV.