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Seneca Valley Virus 2C and 3C(pro) Induce Apoptosis via Mitochondrion-Mediated Intrinsic Pathway

Seneca Valley virus (SVV) is the only member of the genus Senecavirus of the Picornaviridae family. SVV can selectively infect and lyse tumor cells with neuroendocrine features and is used as an oncolytic virus for treating small-cell lung cancers. However, the detailed mechanism underlying SVV-medi...

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Autores principales: Liu, Tingting, Li, Xiangmin, Wu, Mengge, Qin, Liuxing, Chen, Huanchun, Qian, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549803/
https://www.ncbi.nlm.nih.gov/pubmed/31191506
http://dx.doi.org/10.3389/fmicb.2019.01202
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author Liu, Tingting
Li, Xiangmin
Wu, Mengge
Qin, Liuxing
Chen, Huanchun
Qian, Ping
author_facet Liu, Tingting
Li, Xiangmin
Wu, Mengge
Qin, Liuxing
Chen, Huanchun
Qian, Ping
author_sort Liu, Tingting
collection PubMed
description Seneca Valley virus (SVV) is the only member of the genus Senecavirus of the Picornaviridae family. SVV can selectively infect and lyse tumor cells with neuroendocrine features and is used as an oncolytic virus for treating small-cell lung cancers. However, the detailed mechanism underlying SVV-mediated destruction of tumor cells remains unclear. In this study, we found that SVV can increase the proportion of apoptotic 293T cells in a dose- and time-dependent manner. SVV-induced apoptosis was initiated via extrinsic and intrinsic pathways through activation of caspase-3, the activity of which could be attenuated by a pan-caspase inhibitor (Z-VAD-FMK). We confirmed that SVV 2C and 3C(pro) play critical roles in SVV-induced apoptosis. The SVV 2C protein was located solely in the mitochondria and activated caspase-3 to induce apoptosis. SVV 3C(pro) induced apoptosis through its protease activity, which was accompanied by release of cytochrome C into the cytoplasm, but did not directly cleave PARP1.
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spelling pubmed-65498032019-06-12 Seneca Valley Virus 2C and 3C(pro) Induce Apoptosis via Mitochondrion-Mediated Intrinsic Pathway Liu, Tingting Li, Xiangmin Wu, Mengge Qin, Liuxing Chen, Huanchun Qian, Ping Front Microbiol Microbiology Seneca Valley virus (SVV) is the only member of the genus Senecavirus of the Picornaviridae family. SVV can selectively infect and lyse tumor cells with neuroendocrine features and is used as an oncolytic virus for treating small-cell lung cancers. However, the detailed mechanism underlying SVV-mediated destruction of tumor cells remains unclear. In this study, we found that SVV can increase the proportion of apoptotic 293T cells in a dose- and time-dependent manner. SVV-induced apoptosis was initiated via extrinsic and intrinsic pathways through activation of caspase-3, the activity of which could be attenuated by a pan-caspase inhibitor (Z-VAD-FMK). We confirmed that SVV 2C and 3C(pro) play critical roles in SVV-induced apoptosis. The SVV 2C protein was located solely in the mitochondria and activated caspase-3 to induce apoptosis. SVV 3C(pro) induced apoptosis through its protease activity, which was accompanied by release of cytochrome C into the cytoplasm, but did not directly cleave PARP1. Frontiers Media S.A. 2019-05-29 /pmc/articles/PMC6549803/ /pubmed/31191506 http://dx.doi.org/10.3389/fmicb.2019.01202 Text en Copyright © 2019 Liu, Li, Wu, Qin, Chen and Qian. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Liu, Tingting
Li, Xiangmin
Wu, Mengge
Qin, Liuxing
Chen, Huanchun
Qian, Ping
Seneca Valley Virus 2C and 3C(pro) Induce Apoptosis via Mitochondrion-Mediated Intrinsic Pathway
title Seneca Valley Virus 2C and 3C(pro) Induce Apoptosis via Mitochondrion-Mediated Intrinsic Pathway
title_full Seneca Valley Virus 2C and 3C(pro) Induce Apoptosis via Mitochondrion-Mediated Intrinsic Pathway
title_fullStr Seneca Valley Virus 2C and 3C(pro) Induce Apoptosis via Mitochondrion-Mediated Intrinsic Pathway
title_full_unstemmed Seneca Valley Virus 2C and 3C(pro) Induce Apoptosis via Mitochondrion-Mediated Intrinsic Pathway
title_short Seneca Valley Virus 2C and 3C(pro) Induce Apoptosis via Mitochondrion-Mediated Intrinsic Pathway
title_sort seneca valley virus 2c and 3c(pro) induce apoptosis via mitochondrion-mediated intrinsic pathway
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549803/
https://www.ncbi.nlm.nih.gov/pubmed/31191506
http://dx.doi.org/10.3389/fmicb.2019.01202
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