1. Academic Validation
  2. Decreased NHE3 activity and trafficking in TGEV-infected IPEC-J2 cells via the SGLT1-mediated P38 MAPK/AKt2 pathway

Decreased NHE3 activity and trafficking in TGEV-infected IPEC-J2 cells via the SGLT1-mediated P38 MAPK/AKt2 pathway

  • Virus Res. 2020 Apr 15;280:197901. doi: 10.1016/j.virusres.2020.197901.
Yang Yang 1 Qiuhan Yu 1 Han Song 1 Ling Ran 1 Kai Wang 1 Luyi Xie 1 Shilei Huang 1 Zheng Niu 1 Yilin Zhang 1 Zifei Kan 1 Tao Yan 1 Zhenhui Song 2
Affiliations

Affiliations

  • 1 Department of Veterinary Medicine Southwest University Chongqing People's Republic of China, Chongqing 402460, China.
  • 2 Department of Veterinary Medicine Southwest University Chongqing People's Republic of China, Chongqing 402460, China. Electronic address: [email protected].
Abstract

Transmissible gastroenteritis virus (TGEV) primarily replicates in intestinal epithelial cells and causes severe damage to host cells, resulting in diarrhea. Surface NHE3 serves as the key regulatory site controlling electroneutral Na+ absorption. In this study, our results showed that the surface NHE3 content was significantly reduced following TGEV Infection, whereas the total level of protein expression was not significantly changed, and NHE3 activity gradually decreased with prolonged Infection time. We then inhibited SGLT1 expression by lentiviral interference and drug inhibition, respectively. Inhibition studies showed that the level of phosphorylation of the downstream key proteins, MAPKAPK-2 and EZRIN, in the SGLT1-mediated p38MAPK/Akt2 signaling pathway was significantly increased. The surface NHE3 expression was also significantly increased, and NHE3 activity was also significantly enhanced. These results demonstrate that a TGEV Infection can inhibit NHE3 translocation and attenuates sodium-hydrogen exchange activity via the SGLT1-mediated p38MAPK/Akt2 signaling pathway, affecting cellular electrolyte absorption leading to diarrhea.

Keywords

Sodium glucose cotransporters 1; Sodium/hydrogen exchanger 3; Translocation; Transmissible gastroenteritis virus.

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