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Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1
Foot-and-mouth disease virus (FMDV) can result in economical destruction of cloven-hoofed animals. FMDV infection has been reported to induce macroautophagy/autophagy; however, the precise molecular mechanisms of autophagy induction and effect of FMDV capsid protein on autophagy remain unknown. In t...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902195/ https://www.ncbi.nlm.nih.gov/pubmed/29166823 http://dx.doi.org/10.1080/15548627.2017.1405187 |
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author | Sun, Peng Zhang, Shumin Qin, Xiaodong Chang, Xingni Cui, Xiaorui Li, Haitao Zhang, Shuaijun Gao, Huanhuan Wang, Penghua Zhang, Zhidong Luo, Jianxun Li, Zhiyong |
author_facet | Sun, Peng Zhang, Shumin Qin, Xiaodong Chang, Xingni Cui, Xiaorui Li, Haitao Zhang, Shuaijun Gao, Huanhuan Wang, Penghua Zhang, Zhidong Luo, Jianxun Li, Zhiyong |
author_sort | Sun, Peng |
collection | PubMed |
description | Foot-and-mouth disease virus (FMDV) can result in economical destruction of cloven-hoofed animals. FMDV infection has been reported to induce macroautophagy/autophagy; however, the precise molecular mechanisms of autophagy induction and effect of FMDV capsid protein on autophagy remain unknown. In the present study, we report that FMDV infection induced a complete autophagy process in the natural host cells of FMDV, and inhibition of autophagy significantly decreased FMDV production, suggesting that FMDV-induced autophagy facilitates viral replication. We found that the EIF2S1-ATF4 pathway was activated and the AKT-MTOR signaling pathway was inhibited by FMDV infection. We also observed that ultraviolet (UV)-inactivated FMDV can induce autophagy. Importantly, our work provides the first piece of evidence that expression of FMDV capsid protein VP2 can induce autophagy through the EIF2S1-ATF4-AKT-MTOR cascade, and we found that VP2 interacted with HSPB1 (heat shock protein family B [small] member 1) and activated the EIF2S1-ATF4 pathway, resulting in autophagy and enhanced FMDV replication. In addition, we show that VP2 induced autophagy in a variety of mammalian cell lines and decreased aggregates of a model mutant HTT (huntingtin) polyglutamine expansion protein (HTT103Q). Overall, our results demonstrate that FMDV capsid protein VP2 induces autophagy through interaction with HSPB1 and activation of the EIF2S1-ATF4 pathway. |
format | Online Article Text |
id | pubmed-5902195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-59021952018-04-23 Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1 Sun, Peng Zhang, Shumin Qin, Xiaodong Chang, Xingni Cui, Xiaorui Li, Haitao Zhang, Shuaijun Gao, Huanhuan Wang, Penghua Zhang, Zhidong Luo, Jianxun Li, Zhiyong Autophagy Research Papers - Basic Science Foot-and-mouth disease virus (FMDV) can result in economical destruction of cloven-hoofed animals. FMDV infection has been reported to induce macroautophagy/autophagy; however, the precise molecular mechanisms of autophagy induction and effect of FMDV capsid protein on autophagy remain unknown. In the present study, we report that FMDV infection induced a complete autophagy process in the natural host cells of FMDV, and inhibition of autophagy significantly decreased FMDV production, suggesting that FMDV-induced autophagy facilitates viral replication. We found that the EIF2S1-ATF4 pathway was activated and the AKT-MTOR signaling pathway was inhibited by FMDV infection. We also observed that ultraviolet (UV)-inactivated FMDV can induce autophagy. Importantly, our work provides the first piece of evidence that expression of FMDV capsid protein VP2 can induce autophagy through the EIF2S1-ATF4-AKT-MTOR cascade, and we found that VP2 interacted with HSPB1 (heat shock protein family B [small] member 1) and activated the EIF2S1-ATF4 pathway, resulting in autophagy and enhanced FMDV replication. In addition, we show that VP2 induced autophagy in a variety of mammalian cell lines and decreased aggregates of a model mutant HTT (huntingtin) polyglutamine expansion protein (HTT103Q). Overall, our results demonstrate that FMDV capsid protein VP2 induces autophagy through interaction with HSPB1 and activation of the EIF2S1-ATF4 pathway. Taylor & Francis 2018-01-29 /pmc/articles/PMC5902195/ /pubmed/29166823 http://dx.doi.org/10.1080/15548627.2017.1405187 Text en © 2017 Zhidong Zhang and Zhiyong Li. Published with license by Taylor & Francis. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Research Papers - Basic Science Sun, Peng Zhang, Shumin Qin, Xiaodong Chang, Xingni Cui, Xiaorui Li, Haitao Zhang, Shuaijun Gao, Huanhuan Wang, Penghua Zhang, Zhidong Luo, Jianxun Li, Zhiyong Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1 |
title | Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1 |
title_full | Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1 |
title_fullStr | Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1 |
title_full_unstemmed | Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1 |
title_short | Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1 |
title_sort | foot-and-mouth disease virus capsid protein vp2 activates the cellular eif2s1-atf4 pathway and induces autophagy via hspb1 |
topic | Research Papers - Basic Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902195/ https://www.ncbi.nlm.nih.gov/pubmed/29166823 http://dx.doi.org/10.1080/15548627.2017.1405187 |
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