Regional differences in gene expression and pathway activation in porcine intestinal organoids following PEDV infection.
Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic virus that causes severe gastrointestinal disease in neonatal piglets, often leading to high mortality. To advance the study of viral pathogenesis, it is essential to develop an in vitro model that accurately replicates swine enteric coronavirus infections. In this study, we designed a porcine intestinal apical-out organoid culture system that supports viral replication while allowing for long-term culture and experimental manipulation. Using apical-out organoids derived from the duodenum, jejunum, and ileum, we examined region-specific gene expression profiles in response to PEDV infection. Bulk RNA sequencing revealed distinct gene expression patterns, highlighting the regional differences in intestinal physiology during infection. Differential gene expression analysis indicated that each intestinal segment activates specific signaling pathways related to cell survival and antiviral responses following PEDV infection. Functional analyses identified key pathways involved in cell development, signaling, apoptosis, and survival. This study elucidates the mechanisms underlying the differential responses of specific intestinal regions to PEDV, which may inform the selection of optimal models for future PEDV research. In summary, our systematic investigation into the responses of various small intestine segments following PEDV infection provides deeper insights into viral pathogenesis. Overall design: To investigate the effect of PEDV in apical-out organoids of duodenum, jejunum, and ileum of porcine, we conducted RNA sequencing of Mock or PEDV treated apical-out organoid of duodenum, jejunum, and ileum