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Duck Plague Virus Promotes DEF Cell Apoptosis by Activating Caspases, Increasing Intracellular ROS Levels and Inducing Cell Cycle S-Phase Arrest

Background: Duck plague virus (DPV) can induce apoptosis in duck embryo fibroblasts (DEFs) and in infected ducks, but the molecular mechanism of DPV-induced apoptosis remains unknown. Methods: We first used qRT-PCR and a Caspase-Glo assay to determine whether the caspase protein family plays an impo...

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Autores principales: Zhao, Chuankuo, Wang, Mingshu, Cheng, Anchun, Yang, Qiao, Wu, Ying, Jia, Renyong, Zhu, Dekang, Chen, Shun, Liu, Mafeng, Zhao, Xinxin, Zhang, Shaqiu, Liu, Yunya, Yu, Yanling, Zhang, Ling, Tian, Bin, Rehman, Mujeeb Ur, Pan, Leichang, Chen, Xiaoyue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409732/
https://www.ncbi.nlm.nih.gov/pubmed/30813500
http://dx.doi.org/10.3390/v11020196
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author Zhao, Chuankuo
Wang, Mingshu
Cheng, Anchun
Yang, Qiao
Wu, Ying
Jia, Renyong
Zhu, Dekang
Chen, Shun
Liu, Mafeng
Zhao, Xinxin
Zhang, Shaqiu
Liu, Yunya
Yu, Yanling
Zhang, Ling
Tian, Bin
Rehman, Mujeeb Ur
Pan, Leichang
Chen, Xiaoyue
author_facet Zhao, Chuankuo
Wang, Mingshu
Cheng, Anchun
Yang, Qiao
Wu, Ying
Jia, Renyong
Zhu, Dekang
Chen, Shun
Liu, Mafeng
Zhao, Xinxin
Zhang, Shaqiu
Liu, Yunya
Yu, Yanling
Zhang, Ling
Tian, Bin
Rehman, Mujeeb Ur
Pan, Leichang
Chen, Xiaoyue
author_sort Zhao, Chuankuo
collection PubMed
description Background: Duck plague virus (DPV) can induce apoptosis in duck embryo fibroblasts (DEFs) and in infected ducks, but the molecular mechanism of DPV-induced apoptosis remains unknown. Methods: We first used qRT-PCR and a Caspase-Glo assay to determine whether the caspase protein family plays an important role in DPV-induced apoptosis. Then, we used an intracellular ROS detection kit and the mitochondrial probe JC-1 to respectively detect ROS levels and mitochondrial membrane potential (MMP). Finally, flow cytometry was used to detect apoptosis and cell cycle progression. Results: In this study, the mRNA levels and enzymatic activities of caspase-3, caspase-7, caspase-8, and caspase-9 were significantly increased during DPV-induced apoptosis. The caspase inhibitors Z-DEVD-FMK, Z-LEHD-FMK, and Q-VD-Oph could inhibit DPV-induced apoptosis and promote viral replication. Subsequently, a significant decrease in MMP and an increase in the intracellular ROS levels were observed. Further study showed that pretreating infected cells with NAC (a ROS scavenger) decreased the intracellular ROS levels, increased the MMP, inhibited apoptosis, and promoted viral replication. Finally, we showed that DPV infection can cause cell cycle S-phase arrest. Conclusions: This study shows that DPV causes cell cycle S-phase arrest and leads to apoptosis through caspase activation and increased intracellular ROS levels. These findings may be useful for gaining an understanding of the pathogenesis of DPV and the apoptotic pathways induced by α-herpesviruses.
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spelling pubmed-64097322019-04-01 Duck Plague Virus Promotes DEF Cell Apoptosis by Activating Caspases, Increasing Intracellular ROS Levels and Inducing Cell Cycle S-Phase Arrest Zhao, Chuankuo Wang, Mingshu Cheng, Anchun Yang, Qiao Wu, Ying Jia, Renyong Zhu, Dekang Chen, Shun Liu, Mafeng Zhao, Xinxin Zhang, Shaqiu Liu, Yunya Yu, Yanling Zhang, Ling Tian, Bin Rehman, Mujeeb Ur Pan, Leichang Chen, Xiaoyue Viruses Article Background: Duck plague virus (DPV) can induce apoptosis in duck embryo fibroblasts (DEFs) and in infected ducks, but the molecular mechanism of DPV-induced apoptosis remains unknown. Methods: We first used qRT-PCR and a Caspase-Glo assay to determine whether the caspase protein family plays an important role in DPV-induced apoptosis. Then, we used an intracellular ROS detection kit and the mitochondrial probe JC-1 to respectively detect ROS levels and mitochondrial membrane potential (MMP). Finally, flow cytometry was used to detect apoptosis and cell cycle progression. Results: In this study, the mRNA levels and enzymatic activities of caspase-3, caspase-7, caspase-8, and caspase-9 were significantly increased during DPV-induced apoptosis. The caspase inhibitors Z-DEVD-FMK, Z-LEHD-FMK, and Q-VD-Oph could inhibit DPV-induced apoptosis and promote viral replication. Subsequently, a significant decrease in MMP and an increase in the intracellular ROS levels were observed. Further study showed that pretreating infected cells with NAC (a ROS scavenger) decreased the intracellular ROS levels, increased the MMP, inhibited apoptosis, and promoted viral replication. Finally, we showed that DPV infection can cause cell cycle S-phase arrest. Conclusions: This study shows that DPV causes cell cycle S-phase arrest and leads to apoptosis through caspase activation and increased intracellular ROS levels. These findings may be useful for gaining an understanding of the pathogenesis of DPV and the apoptotic pathways induced by α-herpesviruses. MDPI 2019-02-24 /pmc/articles/PMC6409732/ /pubmed/30813500 http://dx.doi.org/10.3390/v11020196 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhao, Chuankuo
Wang, Mingshu
Cheng, Anchun
Yang, Qiao
Wu, Ying
Jia, Renyong
Zhu, Dekang
Chen, Shun
Liu, Mafeng
Zhao, Xinxin
Zhang, Shaqiu
Liu, Yunya
Yu, Yanling
Zhang, Ling
Tian, Bin
Rehman, Mujeeb Ur
Pan, Leichang
Chen, Xiaoyue
Duck Plague Virus Promotes DEF Cell Apoptosis by Activating Caspases, Increasing Intracellular ROS Levels and Inducing Cell Cycle S-Phase Arrest
title Duck Plague Virus Promotes DEF Cell Apoptosis by Activating Caspases, Increasing Intracellular ROS Levels and Inducing Cell Cycle S-Phase Arrest
title_full Duck Plague Virus Promotes DEF Cell Apoptosis by Activating Caspases, Increasing Intracellular ROS Levels and Inducing Cell Cycle S-Phase Arrest
title_fullStr Duck Plague Virus Promotes DEF Cell Apoptosis by Activating Caspases, Increasing Intracellular ROS Levels and Inducing Cell Cycle S-Phase Arrest
title_full_unstemmed Duck Plague Virus Promotes DEF Cell Apoptosis by Activating Caspases, Increasing Intracellular ROS Levels and Inducing Cell Cycle S-Phase Arrest
title_short Duck Plague Virus Promotes DEF Cell Apoptosis by Activating Caspases, Increasing Intracellular ROS Levels and Inducing Cell Cycle S-Phase Arrest
title_sort duck plague virus promotes def cell apoptosis by activating caspases, increasing intracellular ros levels and inducing cell cycle s-phase arrest
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409732/
https://www.ncbi.nlm.nih.gov/pubmed/30813500
http://dx.doi.org/10.3390/v11020196
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