2. Academic Validation
  3. TUDCA inhibits EV71 replication by regulating ER stress signaling pathway and suppressing autophagy

TUDCA inhibits EV71 replication by regulating ER stress signaling pathway and suppressing autophagy

  • Diagn Microbiol Infect Dis. 2024 Aug 22;110(4):116500. doi: 10.1016/j.diagmicrobio.2024.116500.
Siwen Wang 1,  Rui Liu 1,  Yuting Zhou 2,  Jinjin Xu 3,  Airong Su 4,  Datong Zheng 5
Affiliations

Affiliations

  • 1 Molecular Diagnostic Laboratory, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003, PR China; Children's Health Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003, PR China; The Second Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210011, PR China.
  • 2 Children's Health Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003, PR China; The Second Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210011, PR China.
  • 3 Molecular Diagnostic Laboratory, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003, PR China.
  • 4 Molecular Diagnostic Laboratory, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003, PR China. Electronic address: suairong-1@163.com.
  • 5 Molecular Diagnostic Laboratory, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003, PR China; Children's Health Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003, PR China; The Second Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210011, PR China. Electronic address: dtzheng@njmu.edu.cn.
PMID: 39213902 DOI: 10.1016/j.diagmicrobio.2024.116500
Abstract

Tauroursodeoxycholic acid (TUDCA) is a naturally occurring hydrophilic bile acid that alleviates endoplasmic reticulum (ER) stress and inhibits Apoptosis, thereby protecting cells. Previous studies have shown that Enterovirus 71 (EV71) Infection modulates ER stress and induces Autophagy to assist viral replication. This study observed the effects of TUDCA pretreatment on HeLa and Vero cells infected with EV71, finding that TUDCA inhibits EV71 replication in TUDCA pretreated HeLa and Vero cells in a dose-dependent manner. We found that TUDCA pretreatment inhibited EV71 replication by regulating three branches of UPR, that is up-regulated ATF6, down-regulated both PERK and IRE1. The results also indicated that Autophagy which is downstream of UPR, was inhibited either. The results indicate that TUDCA inhibits EV71 replication by regulating UPR sensor proteins and Autophagy following ER stress.

Keywords

Activating transcription factor 6 (ATF6); Autophagy; Endoplasmic reticulum stress (ER stress); Enterovirus 71 (EV71); Inositol-requiring enzyme 1 (IRE1); Protein kinase RNA-like ER kinase (PERK); Tauroursodeoxycholic acid (TUDCA); Unfolded protein response (UPR).

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