Bcl-xL Reduces Chinese Giant Salamander Iridovirus-Induced Mitochondrial Apoptosis by Interacting with Bak and Inhibiting the p53 Pathway

Chinese giant salamander iridovirus (GSIV) infection could lead to mitochondrial apoptosis in this animal, a process that involves B-cell lymphoma-2 (BCL-2) superfamily molecules. The mRNA expression level of Bcl-xL, a crucial antiapoptotic molecule in the BCL-2 family, was reduced in early infectio...

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Autores principales:	Yiqun Li, Yuding Fan, Yong Zhou, Nan Jiang, Mingyang Xue, Yan Meng, Wenzhi Liu, Jingjing Zhang, Ge Lin, Lingbing Zeng
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Bcl-xL chinese giant salamander iridovirus mitochondria apoptosis Bak p53 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/955151ea1b744110b78e674b11944b1e
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spelling	oai:doaj.org-article:955151ea1b744110b78e674b11944b1e2021-11-25T19:13:28ZBcl-xL Reduces Chinese Giant Salamander Iridovirus-Induced Mitochondrial Apoptosis by Interacting with Bak and Inhibiting the p53 Pathway10.3390/v131122241999-4915https://doaj.org/article/955151ea1b744110b78e674b11944b1e2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2224https://doaj.org/toc/1999-4915Chinese giant salamander iridovirus (GSIV) infection could lead to mitochondrial apoptosis in this animal, a process that involves B-cell lymphoma-2 (BCL-2) superfamily molecules. The mRNA expression level of Bcl-xL, a crucial antiapoptotic molecule in the BCL-2 family, was reduced in early infection and increased in late infection. However, the molecular mechanism remains unknown. In this study, the function and regulatory mechanisms of Chinese giant salamander (<i>Andrias davidianus</i>) Bcl-xL (AdBcl-xL) during GSIV infection were investigated. Western blotting assays revealed that the level of Bcl-xL protein was downregulated markedly as the infection progressed. Plasmids expressing <i>AdBcl-xL</i> or <i>AdBcl-xL</i> short interfering RNAs were separately constructed and transfected into Chinese giant salamander muscle cells. Confocal microscopy showed that overexpressed AdBcl-xL was translocated to the mitochondria after infection with GSIV. Additionally, flow cytometry analysis demonstrated that apoptotic progress was reduced in both <i>AdBcl-xL</i>-overexpressing cells compared with those in the control, while apoptotic progress was enhanced in cells silenced for <i>AdBcl-xL</i>. A lower number of copies of virus major capsid protein genes and a reduced protein synthesis were confirmed in <i>AdBcl-xL</i>-overexpressing cells. Moreover, AdBcl-xL could bind directly to the proapoptotic molecule AdBak with or without GSIV infection. In addition, the p53 level was inhibited and the mRNA expression levels of crucial regulatory molecules in the p53 pathway were regulated in <i>AdBcl-xL</i>-overexpressing cells during GSIV infection. These results suggest that AdBcl-xL plays negative roles in GSIV-induced mitochondrial apoptosis and virus replication by binding to AdBak and inhibiting p53 activation.Yiqun LiYuding FanYong ZhouNan JiangMingyang XueYan MengWenzhi LiuJingjing ZhangGe LinLingbing ZengMDPI AGarticleBcl-xLchinese giant salamander iridovirusmitochondriaapoptosisBakp53MicrobiologyQR1-502ENViruses, Vol 13, Iss 2224, p 2224 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bcl-xL chinese giant salamander iridovirus mitochondria apoptosis Bak p53 Microbiology QR1-502
spellingShingle	Bcl-xL chinese giant salamander iridovirus mitochondria apoptosis Bak p53 Microbiology QR1-502 Yiqun Li Yuding Fan Yong Zhou Nan Jiang Mingyang Xue Yan Meng Wenzhi Liu Jingjing Zhang Ge Lin Lingbing Zeng Bcl-xL Reduces Chinese Giant Salamander Iridovirus-Induced Mitochondrial Apoptosis by Interacting with Bak and Inhibiting the p53 Pathway
description	Chinese giant salamander iridovirus (GSIV) infection could lead to mitochondrial apoptosis in this animal, a process that involves B-cell lymphoma-2 (BCL-2) superfamily molecules. The mRNA expression level of Bcl-xL, a crucial antiapoptotic molecule in the BCL-2 family, was reduced in early infection and increased in late infection. However, the molecular mechanism remains unknown. In this study, the function and regulatory mechanisms of Chinese giant salamander (<i>Andrias davidianus</i>) Bcl-xL (AdBcl-xL) during GSIV infection were investigated. Western blotting assays revealed that the level of Bcl-xL protein was downregulated markedly as the infection progressed. Plasmids expressing <i>AdBcl-xL</i> or <i>AdBcl-xL</i> short interfering RNAs were separately constructed and transfected into Chinese giant salamander muscle cells. Confocal microscopy showed that overexpressed AdBcl-xL was translocated to the mitochondria after infection with GSIV. Additionally, flow cytometry analysis demonstrated that apoptotic progress was reduced in both <i>AdBcl-xL</i>-overexpressing cells compared with those in the control, while apoptotic progress was enhanced in cells silenced for <i>AdBcl-xL</i>. A lower number of copies of virus major capsid protein genes and a reduced protein synthesis were confirmed in <i>AdBcl-xL</i>-overexpressing cells. Moreover, AdBcl-xL could bind directly to the proapoptotic molecule AdBak with or without GSIV infection. In addition, the p53 level was inhibited and the mRNA expression levels of crucial regulatory molecules in the p53 pathway were regulated in <i>AdBcl-xL</i>-overexpressing cells during GSIV infection. These results suggest that AdBcl-xL plays negative roles in GSIV-induced mitochondrial apoptosis and virus replication by binding to AdBak and inhibiting p53 activation.
format	article
author	Yiqun Li Yuding Fan Yong Zhou Nan Jiang Mingyang Xue Yan Meng Wenzhi Liu Jingjing Zhang Ge Lin Lingbing Zeng
author_facet	Yiqun Li Yuding Fan Yong Zhou Nan Jiang Mingyang Xue Yan Meng Wenzhi Liu Jingjing Zhang Ge Lin Lingbing Zeng
author_sort	Yiqun Li
title	Bcl-xL Reduces Chinese Giant Salamander Iridovirus-Induced Mitochondrial Apoptosis by Interacting with Bak and Inhibiting the p53 Pathway
title_short	Bcl-xL Reduces Chinese Giant Salamander Iridovirus-Induced Mitochondrial Apoptosis by Interacting with Bak and Inhibiting the p53 Pathway
title_full	Bcl-xL Reduces Chinese Giant Salamander Iridovirus-Induced Mitochondrial Apoptosis by Interacting with Bak and Inhibiting the p53 Pathway
title_fullStr	Bcl-xL Reduces Chinese Giant Salamander Iridovirus-Induced Mitochondrial Apoptosis by Interacting with Bak and Inhibiting the p53 Pathway
title_full_unstemmed	Bcl-xL Reduces Chinese Giant Salamander Iridovirus-Induced Mitochondrial Apoptosis by Interacting with Bak and Inhibiting the p53 Pathway
title_sort	bcl-xl reduces chinese giant salamander iridovirus-induced mitochondrial apoptosis by interacting with bak and inhibiting the p53 pathway
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/955151ea1b744110b78e674b11944b1e
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Bcl-xL Reduces Chinese Giant Salamander Iridovirus-Induced Mitochondrial Apoptosis by Interacting with Bak and Inhibiting the p53 Pathway

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