African Swine Fever Virus pE199L Induces Mitochondrial-Dependent Apoptosis

African swine fever (ASF) is a severe hemorrhagic disease in swine characterized by massive lymphocyte depletion and cell death, with apoptosis and necrosis in infected lymphoid tissues. However, the molecular mechanism regarding ASFV-induced cell death remains largely unknown. In this study, 94 ASF...

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Autores principales:	Tingting Li, Gaihong Zhao, Taoqing Zhang, Zhaoxia Zhang, Xin Chen, Jie Song, Xiao Wang, Jiangnan Li, Li Huang, Lili Wen, Changyao Li, Dongming Zhao, Xijun He, Zhigao Bu, Jun Zheng, Changjiang Weng
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	African swine fever virus pE199L mitochondria apoptosis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/434beddc904542729fe64f0ed90fa948
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spelling	oai:doaj.org-article:434beddc904542729fe64f0ed90fa9482021-11-25T19:13:40ZAfrican Swine Fever Virus pE199L Induces Mitochondrial-Dependent Apoptosis10.3390/v131122401999-4915https://doaj.org/article/434beddc904542729fe64f0ed90fa9482021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2240https://doaj.org/toc/1999-4915African swine fever (ASF) is a severe hemorrhagic disease in swine characterized by massive lymphocyte depletion and cell death, with apoptosis and necrosis in infected lymphoid tissues. However, the molecular mechanism regarding ASFV-induced cell death remains largely unknown. In this study, 94 ASFV-encoded proteins were screened to determine the viral proteins involved in cell death in vitro, and pE199L showed the most significant effect. Ectopic expression of pE199L in porcine cells (CRL-2843) and human cells (HEK293T and HeLa cells) induced cell death remarkably, showing obvious shrinking, blistering, apoptotic bodies, and nuclear DNA fragments. Meanwhile, cell death was markedly alleviated when the expression of pE199L was knocked down during ASFV infection. Additionally, the expression of pE199L caused a loss of mitochondrial membrane potential, release of cytochrome C, and caspase-9 and -3/7 activation, indicating that the mitochondrial apoptotic pathway was involved in pE199L-induced apoptosis. Further investigations showed that pE199L interacted with several anti-apoptotic BCL-2 subfamily members (such as BCL-X<sub>L</sub>, MCL-1, BCL-W, and BCL-2A1) and competed with BAK for BCL-X<sub>L</sub>, which promoted BAK and BAX activation. Taken together, ASFV pE199L induces the mitochondrial-dependent apoptosis, which may provide clues for a comprehensive understanding of ASFV pathogenesis.Tingting LiGaihong ZhaoTaoqing ZhangZhaoxia ZhangXin ChenJie SongXiao WangJiangnan LiLi HuangLili WenChangyao LiDongming ZhaoXijun HeZhigao BuJun ZhengChangjiang WengMDPI AGarticleAfrican swine fever viruspE199LmitochondriaapoptosisMicrobiologyQR1-502ENViruses, Vol 13, Iss 2240, p 2240 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	African swine fever virus pE199L mitochondria apoptosis Microbiology QR1-502
spellingShingle	African swine fever virus pE199L mitochondria apoptosis Microbiology QR1-502 Tingting Li Gaihong Zhao Taoqing Zhang Zhaoxia Zhang Xin Chen Jie Song Xiao Wang Jiangnan Li Li Huang Lili Wen Changyao Li Dongming Zhao Xijun He Zhigao Bu Jun Zheng Changjiang Weng African Swine Fever Virus pE199L Induces Mitochondrial-Dependent Apoptosis
description	African swine fever (ASF) is a severe hemorrhagic disease in swine characterized by massive lymphocyte depletion and cell death, with apoptosis and necrosis in infected lymphoid tissues. However, the molecular mechanism regarding ASFV-induced cell death remains largely unknown. In this study, 94 ASFV-encoded proteins were screened to determine the viral proteins involved in cell death in vitro, and pE199L showed the most significant effect. Ectopic expression of pE199L in porcine cells (CRL-2843) and human cells (HEK293T and HeLa cells) induced cell death remarkably, showing obvious shrinking, blistering, apoptotic bodies, and nuclear DNA fragments. Meanwhile, cell death was markedly alleviated when the expression of pE199L was knocked down during ASFV infection. Additionally, the expression of pE199L caused a loss of mitochondrial membrane potential, release of cytochrome C, and caspase-9 and -3/7 activation, indicating that the mitochondrial apoptotic pathway was involved in pE199L-induced apoptosis. Further investigations showed that pE199L interacted with several anti-apoptotic BCL-2 subfamily members (such as BCL-X<sub>L</sub>, MCL-1, BCL-W, and BCL-2A1) and competed with BAK for BCL-X<sub>L</sub>, which promoted BAK and BAX activation. Taken together, ASFV pE199L induces the mitochondrial-dependent apoptosis, which may provide clues for a comprehensive understanding of ASFV pathogenesis.
format	article
author	Tingting Li Gaihong Zhao Taoqing Zhang Zhaoxia Zhang Xin Chen Jie Song Xiao Wang Jiangnan Li Li Huang Lili Wen Changyao Li Dongming Zhao Xijun He Zhigao Bu Jun Zheng Changjiang Weng
author_facet	Tingting Li Gaihong Zhao Taoqing Zhang Zhaoxia Zhang Xin Chen Jie Song Xiao Wang Jiangnan Li Li Huang Lili Wen Changyao Li Dongming Zhao Xijun He Zhigao Bu Jun Zheng Changjiang Weng
author_sort	Tingting Li
title	African Swine Fever Virus pE199L Induces Mitochondrial-Dependent Apoptosis
title_short	African Swine Fever Virus pE199L Induces Mitochondrial-Dependent Apoptosis
title_full	African Swine Fever Virus pE199L Induces Mitochondrial-Dependent Apoptosis
title_fullStr	African Swine Fever Virus pE199L Induces Mitochondrial-Dependent Apoptosis
title_full_unstemmed	African Swine Fever Virus pE199L Induces Mitochondrial-Dependent Apoptosis
title_sort	african swine fever virus pe199l induces mitochondrial-dependent apoptosis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/434beddc904542729fe64f0ed90fa948
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African Swine Fever Virus pE199L Induces Mitochondrial-Dependent Apoptosis

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