PMID- 33581126 OWN - NLM STAT- MEDLINE DCOM- 20210317 LR - 20211204 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 271 DP - 2021 Apr 15 TI - Enterovirus 71 induces autophagy in mice via mTOR inhibition and ERK pathway activation. PG - 119188 LID - S0024-3205(21)00173-9 [pii] LID - 10.1016/j.lfs.2021.119188 [doi] AB - AIMS: Enterovirus 71 (EV71) is one of the main viruses that cause hand-foot-mouth disease; however, its pathogenic mechanism remains unclear. This study characterized the relationship between EV71 infection and autophagy in vivo and explored the molecular mechanism underlying EV71-induced autophagy. MATERIALS AND METHODS: A mouse model of EV71 infection was prepared by intraperitoneally injecting one-day-old BALB/c suckling mice with 30 muL/g of EV71 virus stock solution for 3 days. The behavior, fur condition, weight, and mice mortality were monitored, and disease scores were calculated. The pathological damage to the brain, lung, and muscle tissues after the viral infection was assessed by hematoxylin and eosin staining. Western blot and immunofluorescence analyses were used to detect the expression levels of viral protein 1, Beclin-1, microtubule-associated protein light chain 3B, mammalian target of rapamycin (mTOR), phosphorylated (p)-mTOR, extracellular signal-regulated protein kinase (ERK) 1/2, and p-ERK. KEY FINDINGS: EV71 infection can trigger autophagy in the brains, lungs, and muscles of infected mice. The autophagy response triggered by EV71 is achieved by the simultaneous mTOR inhibition and the ERK pathway activation. Blocking the mTOR pathway may aggravate autophagy, whereas ERK inhibition alleviates autophagy but cannot completely prevent it. SIGNIFICANCE: EV71 infection can induce autophagy in mice, involving mTOR and ERK signaling pathways. These two signaling pathways are independent and do not interfere with each other. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Wang, Baixin AU - Wang B AD - School of Basic Medicine, Jiamusi University, Jiamusi 154007, China. FAU - Zhu, Yuanzhi AU - Zhu Y AD - School of Basic Medicine, Jiamusi University, Jiamusi 154007, China. FAU - Liu, Lei AU - Liu L AD - School of Basic Medicine, Jiamusi University, Jiamusi 154007, China. FAU - Wang, Binshan AU - Wang B AD - School of Basic Medicine, Jiamusi University, Jiamusi 154007, China. FAU - Chen, Mei AU - Chen M AD - School of Basic Medicine, Jiamusi University, Jiamusi 154007, China. FAU - Wang, Jingtao AU - Wang J AD - School of Basic Medicine, Jiamusi University, Jiamusi 154007, China. FAU - Yang, Limin AU - Yang L AD - School of Medicine, Dalian University, Dalian 116622, China. Electronic address: yanglimin@dlu.edu.cn. FAU - Liu, JiGuang AU - Liu J AD - School of Basic Medicine, Jiamusi University, Jiamusi 154007, China. Electronic address: 13694668555@163.com. LA - eng PT - Journal Article DEP - 20210211 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Animals, Newborn MH - Autophagy/*physiology MH - Cell Line, Tumor MH - Enterovirus A, Human/*metabolism MH - Enterovirus Infections/*metabolism/pathology MH - Enzyme Activation/physiology MH - Female MH - Humans MH - MAP Kinase Signaling System/*physiology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - TOR Serine-Threonine Kinases/*antagonists & inhibitors/*metabolism OTO - NOTNLM OT - Autophagy OT - Enterovirus 71 OT - Extracellular signal-regulated kinase OT - Hand-foot-mouth disease OT - Mammalian target of rapamycin EDAT- 2021/02/14 06:00 MHDA- 2021/03/18 06:00 CRDT- 2021/02/13 20:09 PHST- 2020/10/25 00:00 [received] PHST- 2021/02/01 00:00 [revised] PHST- 2021/02/02 00:00 [accepted] PHST- 2021/02/14 06:00 [pubmed] PHST- 2021/03/18 06:00 [medline] PHST- 2021/02/13 20:09 [entrez] AID - S0024-3205(21)00173-9 [pii] AID - 10.1016/j.lfs.2021.119188 [doi] PST - ppublish SO - Life Sci. 2021 Apr 15;271:119188. doi: 10.1016/j.lfs.2021.119188. Epub 2021 Feb 11.