Decreased NHE3 activity in intestinal epithelial cells in TGEV and PEDV-induced piglet diarrhea

Transmissible gastroenteritis (TGE) and porcine epidemic diarrhea (PED) are highly transmissible intestinal infections caused by transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV), respectively. They are clinically associated with vomiting, diarrhea, and dehydration in piglets. An imbalance in Na⁺ uptake by intestinal epithelial cells causes TGEV/PEDV-induced diarrhea. However, the mechanism by which TGEV/PEDV-infection in piglets causes Na⁺ imbalance diarrhea has not been elucidated. In the present study, we demonstrated that specific inhibition of NHE3 activity caused small intestinal bulging, intestinal wall thinning and severe diarrhea in piglets, consistent with the signs of TGEV/PEDV infection. This study further elucidated the role of NHE3 in TGEV/PEDV-induced diarrhea. In this study, small intestinal epithelial cells (IPEC-J2) were used as a model of infection. The results showed that TGEV/PEDV infection reduced NHE3 activity and Na⁺ uptake in IPEC-J2 cells. Further studies revealed that the use of NHE3-specific inhibitors could reduce the amount of cell membrane NHE3, thereby decreasing Na⁺ uptake and ultimately leading to diarrhea. Transcriptomic studies performed on obtained jejunal tissues were also consistent with pre-laboratory results. This study will provide a basis for understanding Na⁺ imbalance diarrhea caused by TGEV/PEDV, as well as for elucidating the diarrheal pathogenesis of other members of α-animal coronaviruses.