Metabolite of Clostridium perfringens type A, palmitic acid, enhances porcine enteric coronavirus porcine epidemic diarrhea virus infection

The host intestinal microbiota has emerged as the third element in the interactions between hosts and enteric viruses, and potentially affects the infection processes of enteric viruses. However, the interaction of porcine enteric coronavirus with intestinal microorganisms during infection remains unclear. In this study, we used 16S-rRNA-based Illumina NovaSeq high-throughput sequencing to identify the changes in the intestinal microbiota of piglets mediated by porcine epidemic diarrhea virus (PEDV) infection and the effects of the alterations in intestinal bacteria on PEDV infection and its molecular mechanisms. The intestinal microbiota of PEDV-infected piglets had significantly less diversity than the healthy group and different bacterial community characteristics. Among the altered intestinal bacteria, the relative abundance of Clostridium perfringens was significantly increased in the PEDV-infected group. A strain of C. perfringens type A, named DQ21, was successfully isolated from the intestines of healthy piglets. The metabolites of swine C. perfringens type A strain DQ21 significantly enhanced PEDV replication in porcine intestinal epithelial cell clone J2 (IPEC-J2) cells, and PEDV infection and pathogenicity in suckling piglets. Palmitic acid (PA) was identified as one of those metabolites with metabolomic technology, and significantly enhanced PEDV replication in IPEC-J2 cells and PEDV infection and pathogenicity in suckling piglets. PA also increased the neutralizing antibody titer in the immune sera of mice. Furthermore, PA mediated the palmitoylation of the PEDV S protein, which improved virion stability and membrane fusion, thereby enhancing viral infection. Overall, our study demonstrates a novel mechanism of PEDV infection, with implications for PEDV pathogenicity.