Transmissible Gastroenteritis Virus Nucleocapsid Protein Interacts with Na + /H + Exchanger 3 To Reduce Na + /H + Exchanger Activity and Promote Piglet Diarrhea

• DOI: 10.1128/jvi.01473-22
• Publication Date: 2022-11-07T15:23:26Z
• Authors: Zheng Niu; ShaSha Xu; YiLing Zhang; ZiFei Kan; JingYi Zhang; Xiangyang Liu; ShuJuan Zhang; Hong Zou; ZhenHui Song
• Keywords: Coronaviridae; Coronavirus

Transmissible gastroenteritis virus (TGEV) is member of the family Coronaviridae and mainly causes acute diarrhea. TGEV infection characterized by vomiting, watery diarrhea, severe dehydration, resulting in high mortality rates neonatal piglets. symptoms are related to an imbalance sodium absorption small intestinal epithelial cells; however, etiology diarrhea caused remains unclear. In this study, we performed transcriptomic analysis tissues from infected healthy piglets observed that expression NHE3, encoding Na+/H+ exchanger 3 (NHE3), main electroneutral cells, was significantly reduced upon infection. We also showed specific inhibition NHE3 activity could lead development Furthermore, revealed interaction between N protein near nucleus. The binding directly affected on cell surface cellular electrolyte absorption, leading Molecular docking computer-aided screening techniques were used screen for blocker which identified irinotecan. then demonstrated irinotecan effective relieving TGEV-induced These findings provide new insights into mechanism design novel antiviral strategies against TGEV. IMPORTANCE A variety coronaviruses have been found cause hosts, including TGEV; pathogenic not clear. Therefore, prompt determination identification efficient therapeutic agents required, both public health reasons economic development. major expressed NHEs intestine, its decreased nearly 70% after Also, resulted This plays important role addition, regulates through protein-protein interaction, essential promote other block Thus, our results a basis guidance drugs diarrhea-causing coronaviruses.