Integrated intestinal response to swine enteric coronaviruses in a piglet model: Exploring clinical, morphological, and microRNA-target gene dynamics during primary infection and rechallenge.

Swine enteric coronaviruses (CoVs) are causes of enteric disease in pigs, characterised by acute watery diarrhoea, more severe in piglets under 7 days of age. Small non-coding RNAs (miRNAs) have been implicated in the regulation of host immune responses during viral infections; however, their involvement in the intestinal response to CoVs infection and reinfection remains poorly understood. For this purpose, 48 four-week-old, weaned piglets were allocated into four experimental groups (n = 12). Groups B, C, and D were orally inoculated with PEDV, SeCoV, or rPEDV-SeCoV strain, respectively, while group A (control) received sterile buffer. Twenty days later, all groups were challenged with rPEDV-SeCoV strain. Clinical signs, growth performance, intestinal viral load, intestinal histomorphometry, and the expression of selected miRNAs and immune-related genes were analysed in duodenum and jejunum. Primary infection was associated with higher viral load, reduced villus height, and decreased average daily gain (ADG), whereas rechallenge resulted in lower viral load, reduced intestinal damage and limited impact on growth performance. At the molecular level, miR-124, miR-146, miR-223, and miR-27b tended to increase following rechallenge, in line with their previously described immunomodulatory functions, whereas miR-15b and miR-155 were associated with IFNG induction, suggesting an association with IFNG-related antiviral responses. These miRNA patterns were accompanied by IL8 expression dynamics, highlighting their involvement in the inflammatory response. Overall, these findings provide new insights into the intestinal immune responses to CoVs infection and reinfection and highlight the involvement of miRNA-mediated regulatory networks in shaping host responses to enteric coronavirus infection in pigs.