PT  - JOURNAL ARTICLE
AU  - Pei-qing Li
AU  - Si-da Yang
AU  - Dan-dan Hu
AU  - Dan WeEI
AU  - Jing Lu
AU  - Huan-ying Zheng
AU  - Shu-shan Nie
AU  - Guang-ming Liu
AU  - Hao-mei Yang
TI  - Enterovirus 71 structural viral protein 1 promotes mouse Schwann cell autophagy via endoplasmic reticulum stress-mediated peripheral myelin protein 22 upregulation
AID  - 10.1101/314468
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 314468
4099  - http://biorxiv.org/content/early/2018/05/04/314468.short
4100  - http://biorxiv.org/content/early/2018/05/04/314468.full
AB  - Enterovirus 71 (EV71) accounts for the majority of hand, foot and mouth disease-related deaths due to fatal neurological complications. The clinical observations and animal models found the early invasion of nervous system, and the demyelinating phenomenon was observed. As one of the receptors of EV71 structural viral protein 1 (VP1), SCARB2 mainly exists on the myelin sheath. EV71 VP1 can promote viral replication through inducing autophagy in neuron cells. This study aims to investigate the role and mechanism of VP1 in autophagy of mouse Schwann cells (MSCs). An EV71 VP1-expressing vector (pEGFP-C3-VP1) was generated and transfected into MSCs. Transmission electron microscopy (TEM) and Western blot analysis of the autophagy marker microtubule-associated proteins 1A/1B light chain 3B (LC3B) were used to assess autophagy in the cells. Real-time PCR and immunofluorescent staining were performed to determine the expression of PMP22. Small interfering RNA against PMP22 was employed to investigate the role of PMP22 in MSCs autophagy. Selective endoplasmic reticulum (ER) stress inhibitor salubrinal (SAL) was employed to determine whether PMP22 is mediated by ER stress. Our results demonstrated that VP1 played a promotive role in MSC autophagy. Overexpression of VP1 upregulated PMP22. PMP22 deficiency downregulated LC3B and thus inhibited autophagy. Furthermore, PMP22 expression was significantly suppressed by SAL. VP1 promotes MSC autophagy through upregulating ER stress-mediated PMP22 expression. VP1/ER stress/ PMP22 axis in autophagy may be a potential therapeutic target for EV71 infection-induced fatal neuronal damage.