PEDV infection downregulates goblet cell differentiation through activating the Notch pathway

Porcine epidemic diarrhoea virus (PEDV) is the most widespread porcine coronavirus worldwide, causing high mortality and a high incidence rate among piglets. The molecular mechanisms by which PEDV regulates epithelial cell function and differentiation, as well as its disruption of the intestinal mucosal barrier, are not yet fully understood. This study reveals that PEDV infection reduces the number of goblet cells and impairs the intestinal barrier integrity in newborn piglets. Regarding the pathways involved in the differentiation of intestinal stem cells (ISCs), PEDV infection concurrently activates the Notch and MAPK pathways while suppressing the Wnt/β-catenin pathway in the intestines of piglets. Furthermore, in vitro experiments using intestinal monolayer organoid models showed that PEDV infection hinders goblet cell differentiation by activating the Notch signalling pathway. Additionally, the PEDV-encoded ORF3 protein, which is crucial for activating the Notch pathway, inhibits goblet cell differentiation in PEDV-infected intestinal monolayer organoids. This study offers new insights into the mechanisms underlying intestinal mucosal barrier dysfunction induced by PEDV infection.