title: Glucocorticoids Prevent Enterovirus 71 Capsid Protein VP1 Induced Calreticulin Surface Exposure by Alleviating Neuronal ER Stress.
abstract: 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.
authors.affiliation: Department of Anatomy Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.|Guangzhou Women and Children's Medical Center, Guangzhou, 510623, Guangdong, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Hu
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou, 510623, Guangdong, China.
authors.forename: Jian-Ning
authors.initials: JN
authors.lastname: Mai
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou, 510623, Guangdong, China.
authors.forename: Li-Ya
authors.initials: LY
authors.lastname: He
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou, 510623, Guangdong, China.
authors.forename: Pei-Qing
authors.initials: PQ
authors.lastname: Li
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou, 510623, Guangdong, China.
authors.forename: Wen-Xiong
authors.initials: WX
authors.lastname: Chen
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou, 510623, Guangdong, China.
authors.forename: Jian-Jiang
authors.initials: JJ
authors.lastname: Yan
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou, 510623, Guangdong, China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Zhu
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou, 510623, Guangdong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Deng
authors.affiliation: First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wei
authors.affiliation: United Family Healthcare Guangzhou Clinic, Guangzhou, 510600, China.
authors.forename: Di-Hui
authors.initials: DH
authors.lastname: Liu
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou, 510623, Guangdong, China. sidayang@gmail.com.
authors.forename: Si-Da
authors.initials: SD
authors.lastname: Yang
authors.affiliation: Department of Anatomy Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. yaozb_sysu@sina.com.
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Yao
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D001933:Brain Stem / Q000187:drug effects / Q000503:physiopathology; D037282:Calreticulin / Q000378:metabolism*; D036022:Capsid Proteins / Q000633:toxicity*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009474:Neurons / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D015854:Up-Regulation; D015678:Viral Structural Proteins / Q000633:toxicity*
chemical_list: D037282:Calreticulin; D036022:Capsid Proteins; C442501:VP1 protein, Foot-and-mouth disease virus; C442459:VP2 protein, Foot-and-mouth disease virus; C442460:VP3 protein, Foot-and-mouth disease virus; C000623164:VP4 protein, Foot-and-mouth disease virus; D015678:Viral Structural Proteins; D003907:Dexamethasone
keywords: Calreticulin; Enterovirus 71; Glucocorticoids; Hand-foot-and-mouth disease