Innate Immune Evasion of Porcine Epidemic Diarrhea Virus Through miRNA‐193a‐5p/IL22/pBD1 Pathway in Intestinal Epithelium

Porcine epidemic diarrhea (PED) virus (PEDV) is a highly contagious intestinal infection that primarily affects suckling pigs. The interaction about the innate immune evasion of PEDV in intestinal epithelium and microRNA (miRNA) remains unclear. A strain of PEDV belonging to the G2a genotype, designated FJND 2022, was successfully isolated and confirmed. Then, the miRNA profile in exosomes‐derived from intestinal porcine epithelial cell line (IPEC) infected with PEDV FJND 2022 for 48 h was evaluated. In exosomes from PEDV‐infected IPECs, 34 miRNAs showed differential expression relative to blank cells. A total of 7762 target genes of those differentially expressed miRNAs were forecast, and the miR‐193a‐5P and its target mRNA interleukin (IL)22 and porcine β‐defensin 1 (pBD1) attracted our interest. After infection with PEDV for 48 h, the mRNA levels and protein levels of IL22 and pBD1 were both notably downregulated, while the mRNA level of miR‐193a‐5P was significantly decreased. When IPECs were pretreated with the mimic of miR‐193a‐5P and then infected with PEDV, the mRNA levels of IL22 and pBD1 were significantly increased while the viral load of PEDV was significantly reduced. However, siRNA‐mediated knockdown of IL22 abrogated the capacity of miR‐193a‐5p mimic pretreatment to restore pBD1 expression. Furthermore, the inhibitor of miR‐193a‐5P was pretreated with IPECs infected with PEDV, resulting in a notable downregulation of IL22 and pBD1 expression, and a significant upregulation of the virus load of PEDV. Finally, we also found that the expression levels of IL22, pBD1, and miR‐193a‐5P were notably reduced in the small intestinal epithelium of suckling piglets infected with PEDV for 48 h. Therefore, in this study we reveal that PEDV downregulates the miR‐193a‐5P expression in the intestinal epithelium to evade the antivirus of IL22/pBD1, which provides new insights into PEDV molecular pathogenesis and immune evasion mechanisms.