Enterovirus 71 VP1 promotes mouse Schwann cell autophagy via ER stress‑mediated PMP22 upregulation

Li,Peiqing; Yang,Sida; Hu,Dandan; Wei,Dan; Lu,Jing; Zheng,Huanying; Nie,Shushan; Liu,Guangming; Yang,Haomei

doi:10.3892/ijmm.2019.4218

Enterovirus 71 VP1 promotes mouse Schwann cell autophagy via ER stress‑mediated PMP22 upregulation

Authors:
- Peiqing Li
- Sida Yang
- Dandan Hu
- Dan Wei
- Jing Lu
- Huanying Zheng
- Shushan Nie
- Guangming Liu
- Haomei Yang
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Affiliations: Department of Pediatric Emergency, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, P.R. China, Department of Pediatric Neurology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, P.R. China, Paediatric Intensive Care Unit, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, Guangdong 511430, P.R. China
Published online on: May 30, 2019 https://doi.org/10.3892/ijmm.2019.4218
Pages: 759-767

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Abstract

Enterovirus 71 (EV71) accounts for the majority of hand, foot and mouth disease‑related deaths due to fatal neurological complications. EV71 structural viral protein 1 (VP1) promotes viral replication by inducing autophagy in neuron cells, but the effect of VP1 on myelin cells is unclear. The present study aimed to investigate the role and mechanism of VP1 in autophagy of mouse Schwann cells. An EV71 VP1‑expressing vector (pEGFP‑C3‑VP1) was generated and transfected into mouse Schwann cells. Transmission electron microscopy and western blot analysis for microtubule‑associated protein 1 light chain 3 α (LC3) II (an autophagy marker) were used to assess autophagy. Reverse transcription‑quantitative PCR and immunofluorescence were performed to determine the expression of peripheral myelin protein 22 (PMP22). Small interfering RNA against PMP22 was used to investigate the role of PMP22 in mouse Schwann cell autophagy. Salubrinal [a selective endoplasmic reticulum (ER) stress inhibitor] was used to determine whether PMP22 expression was affected by ER stress. The present results indicated that VP1 promoted mouse Schwann cell autophagy. Overexpression of VP1 upregulated PMP22. PMP22 deficiency downregulated LC3II and thus inhibited autophagy. Furthermore, PMP22 expression was significantly suppressed by salubrinal. In conclusion, VP1 promoted mouse Schwann cell autophagy through upregulation of ER stress‑mediated PMP22 expression. Therefore, the VP1/ER stress/PMP22 autophagy axis may be a potential therapeutic target for EV71 infection‑induced fatal neuronal damage.

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