Coxsackievirus B3 Infection Triggers Autophagy through 3 Pathways of Endoplasmic Reticulum Stress.

Xiao Nuan Luo; Hai Lan Yao; Juan Song; Qin Qin Song; Bing Tian Shi; Dong Xia; Jun Han

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Coxsackievirus B3 Infection Triggers Autophagy through 3 Pathways of Endoplasmic Reticulum Stress.

Author: Xiao Nuan LUO ¹ ; Hai Lan YAO ² ; Juan SONG ¹ ; Qin Qin SONG ¹ ; Bing Tian SHI ¹ ; Dong XIA ¹ ; Jun HAN ¹
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1. State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
2. Molecular Immunology Laboratory, Capital Institute of Pediatrics, Beijing 100020, China.
Publication Type:Journal Article
Keywords: Autophagy; Coxsackievirus B3 (CVB3); Endoplasmic reticulum (ER) stress; Unfolded protein response (UPR)
MeSH: Activating Transcription Factor 6; metabolism; Autophagy; Coxsackievirus Infections; metabolism; Endoplasmic Reticulum Stress; Endoribonucleases; metabolism; Enterovirus B, Human; HeLa Cells; Humans; Protein-Serine-Threonine Kinases; metabolism; Signal Transduction; eIF-2 Kinase; metabolism
From: Biomedical and Environmental Sciences 2018;31(12):867-875
CountryChina
Language:English
Abstract: OBJECTIVE:Autophagy is a highly conserved intracellular degradation pathway. Many picornaviruses induce autophagy to benefit viral replication, but an understanding of how autophagy occurs remains incomplete. In this study, we explored whether coxsackievirus B3 (CVB3) infection induced autophagy through endoplasmic reticulum (ER) stress.
METHODS:In CVB3-infected HeLa cells, the specific molecules of ER stress and autophagy were detected using Western blotting, reverse transcription polymerase chain reaction (RT-PCR), and confocal microscopy. Then PKR-like ER protein kinase (PERK) inhibitor, inositol-requiring protein-1 (IRE1) inhibitor, or activating transcription factor-6 (ATF6) inhibitor worked on CVB3-infected cells, their effect on autophagy was assessed by Western blotting for detecting microtubule-associated protein light chain 3 (LC3).
RESULTS:CVB3 infection induced ER stress, and ER stress sensors PERK/eIF2α, IRE1/XBP1, and ATF6 were activated. CVB3 infection increased the accumulation of green fluorescent protein (GFP)-LC3 punctuation and induced the conversion from LC3-I to phosphatidylethanolamine-conjugated LC3-1 (LC3-II). CVB3 infection still decreased the expression of mammalian target of rapamycin (mTOR) and p-mTOR. Inhibition of PERK, IRE1, or ATF6 significantly decreased the ratio of LC3-II to LC3-I in CVB3-infected HeLa cells.
CONCLUSION:CVB3 infection induced autophagy through ER stress in HeLa cells, and PERK, IRE1, and ATF6a pathways participated in the regulation of autophagy. Our data suggested that ER stress may inhibit mTOR signaling pathway to induce autophagy during CVB3 infection.