Glucocorticoids Prevent Enterovirus 71 Capsid Protein VP1 Induced Calreticulin Surface Exposure by Alleviating Neuronal ER Stress

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• 作者：Dan-Dan Hu ; Jian-Ning Mai ; Li-Ya He ; Pei-Qing Li ; Wen-Xiong Chen…
• 关键词：Hand ; foot ; and ; mouth disease ; Enterovirus 71 ; Calreticulin ; Glucocorticoids
• 刊名：Neurotoxicity Research
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：31
• 期：2
• 页码：204-217
• 全文大小：
• 刊物主题：Neurosciences; Neurology; Neurochemistry; Pharmacology/Toxicology; Neurobiology; Cell Biology;
• 出版者：Springer US
• ISSN：1476-3524
• 卷排序：31

文摘

Severe hand-foot-and-mouth disease (HFMD) caused by Enterovirus 71 (EV71) always accompanies with inflammation and neuronal damage in the central nervous system (CNS). During neuronal injuries, cell surface-exposed calreticulin (Ecto-CRT) is an important mediator for primary phagocytosis of viable neurons by microglia. Our data confirmed that brainstem neurons underwent neuronophagia by glia in EV71-induced death cases of HFMD. EV71 capsid proteins VP1, VP2, VP3, or VP4 did not induce apoptosis of brainstem neurons. Interestingly, we found VP1-activated endoplasmic reticulum (ER) stress and autophagy could promote Ecto-CRT upregulation, but ER stress or autophagy alone was not sufficient to induce CRT exposure. Furthermore, we demonstrated that VP1-induced autophagy activation was mediated by ER stress. Meaningfully, we found dexamethasone treatment could attenuate Ecto-CRT upregulation by alleviating VP1-induced ER stress. Altogether, these findings identify VP1-promoted Ecto-CRT upregulation as a novel mechanism of EV71-induced neuronal cell damage and highlight the potential of the use of glucocorticoids to treat severe HFMD patients with CNS complications.