Protein 2B of Coxsackievirus B3 Induces Autophagy Relying on Its Transmembrane Hydrophobic Sequences
Coxsackievirus B (CVB) belongs to Enterovirus genus within the Picornaviridae family, and it is one of the most common causative pathogens of viral myocarditis in young adults. The pathogenesis of myocarditis caused by CVB has not been completely elucidated. In CVB infection, autophagy is manipulate...
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doaj-6749d4da20004845a718133ae1657bda2020-11-24T22:26:08ZengMDPI AGViruses1999-49152016-05-018513110.3390/v8050131v8050131Protein 2B of Coxsackievirus B3 Induces Autophagy Relying on Its Transmembrane Hydrophobic SequencesHeng Wu0Xia Zhai1Yang Chen2Ruixue Wang3Lexun Lin4Sijia Chen5Tianying Wang6Xiaoyan Zhong7Xiaoyu Wu8Yan Wang9Fengmin Zhang10Wenran Zhao11Zhaohua Zhong12Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, ChinaDepartment of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, ChinaDepartment of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, ChinaDepartment of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, ChinaDepartment of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, ChinaDepartment of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, ChinaDepartment of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, ChinaDepartment of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, ChinaDepartment of Cardiology, The First Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001, ChinaDepartment of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, ChinaDepartment of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, ChinaDepartment of Cell Biology, Harbin Medical University, 157 Baojian Road, Harbin 150081, ChinaDepartment of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, ChinaCoxsackievirus B (CVB) belongs to Enterovirus genus within the Picornaviridae family, and it is one of the most common causative pathogens of viral myocarditis in young adults. The pathogenesis of myocarditis caused by CVB has not been completely elucidated. In CVB infection, autophagy is manipulated to facilitate viral replication. Here we report that protein 2B, one of the non-structural proteins of CVB3, possesses autophagy-inducing capability. The autophagy-inducing motif of protein 2B was identified by the generation of truncated 2B and site-directed mutagenesis. The expression of 2B alone was sufficient to induce the formation of autophagosomes in HeLa cells, while truncated 2B containing the two hydrophobic regions of the protein also induced autophagy. In addition, we demonstrated that a single amino acid substitution (56V→A) in the stem loop in between the two hydrophobic regions of protein 2B abolished the formation of autophagosomes. Moreover, we found that 2B and truncated 2B with autophagy-inducting capability were co-localized with LC3-II. This study indicates that protein 2B relies on its transmembrane hydrophobic regions to induce the formation of autophagosomes, while 56 valine residue in the stem loop of protein 2B might exert critical structural influence on its two hydrophobic regions. These results may provide new insight for understanding the molecular mechanism of autophagy triggered by CVB infection.http://www.mdpi.com/1999-4915/8/5/131coxsackievirus B3autophagyprotein 2Btransmembrane hydrophobic sequence |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Heng Wu Xia Zhai Yang Chen Ruixue Wang Lexun Lin Sijia Chen Tianying Wang Xiaoyan Zhong Xiaoyu Wu Yan Wang Fengmin Zhang Wenran Zhao Zhaohua Zhong |
spellingShingle |
Heng Wu Xia Zhai Yang Chen Ruixue Wang Lexun Lin Sijia Chen Tianying Wang Xiaoyan Zhong Xiaoyu Wu Yan Wang Fengmin Zhang Wenran Zhao Zhaohua Zhong Protein 2B of Coxsackievirus B3 Induces Autophagy Relying on Its Transmembrane Hydrophobic Sequences Viruses coxsackievirus B3 autophagy protein 2B transmembrane hydrophobic sequence |
author_facet |
Heng Wu Xia Zhai Yang Chen Ruixue Wang Lexun Lin Sijia Chen Tianying Wang Xiaoyan Zhong Xiaoyu Wu Yan Wang Fengmin Zhang Wenran Zhao Zhaohua Zhong |
author_sort |
Heng Wu |
title |
Protein 2B of Coxsackievirus B3 Induces Autophagy Relying on Its Transmembrane Hydrophobic Sequences |
title_short |
Protein 2B of Coxsackievirus B3 Induces Autophagy Relying on Its Transmembrane Hydrophobic Sequences |
title_full |
Protein 2B of Coxsackievirus B3 Induces Autophagy Relying on Its Transmembrane Hydrophobic Sequences |
title_fullStr |
Protein 2B of Coxsackievirus B3 Induces Autophagy Relying on Its Transmembrane Hydrophobic Sequences |
title_full_unstemmed |
Protein 2B of Coxsackievirus B3 Induces Autophagy Relying on Its Transmembrane Hydrophobic Sequences |
title_sort |
protein 2b of coxsackievirus b3 induces autophagy relying on its transmembrane hydrophobic sequences |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2016-05-01 |
description |
Coxsackievirus B (CVB) belongs to Enterovirus genus within the Picornaviridae family, and it is one of the most common causative pathogens of viral myocarditis in young adults. The pathogenesis of myocarditis caused by CVB has not been completely elucidated. In CVB infection, autophagy is manipulated to facilitate viral replication. Here we report that protein 2B, one of the non-structural proteins of CVB3, possesses autophagy-inducing capability. The autophagy-inducing motif of protein 2B was identified by the generation of truncated 2B and site-directed mutagenesis. The expression of 2B alone was sufficient to induce the formation of autophagosomes in HeLa cells, while truncated 2B containing the two hydrophobic regions of the protein also induced autophagy. In addition, we demonstrated that a single amino acid substitution (56V→A) in the stem loop in between the two hydrophobic regions of protein 2B abolished the formation of autophagosomes. Moreover, we found that 2B and truncated 2B with autophagy-inducting capability were co-localized with LC3-II. This study indicates that protein 2B relies on its transmembrane hydrophobic regions to induce the formation of autophagosomes, while 56 valine residue in the stem loop of protein 2B might exert critical structural influence on its two hydrophobic regions. These results may provide new insight for understanding the molecular mechanism of autophagy triggered by CVB infection. |
topic |
coxsackievirus B3 autophagy protein 2B transmembrane hydrophobic sequence |
url |
http://www.mdpi.com/1999-4915/8/5/131 |
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