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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MDPI AG
2021-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/11/2224 |
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| 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 |
| collection | DOAJ |
| 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. |
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| format | Article |
| id | doaj.art-955151ea1b744110b78e674b11944b1e |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T04:59:20Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-955151ea1b744110b78e674b11944b1e2023-11-23T01:57:00ZengMDPI AGViruses1999-49152021-11-011311222410.3390/v13112224Bcl-xL Reduces Chinese Giant Salamander Iridovirus-Induced Mitochondrial Apoptosis by Interacting with Bak and Inhibiting the p53 PathwayYiqun Li0Yuding Fan1Yong Zhou2Nan Jiang3Mingyang Xue4Yan Meng5Wenzhi Liu6Jingjing Zhang7Ge Lin8Lingbing Zeng9Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, ChinaYangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, ChinaYangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, ChinaYangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, ChinaYangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, ChinaYangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, ChinaYangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, ChinaYangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, ChinaYangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, ChinaYangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, ChinaChinese 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.https://www.mdpi.com/1999-4915/13/11/2224Bcl-xLchinese giant salamander iridovirusmitochondriaapoptosisBakp53 |
| spellingShingle | 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 Viruses Bcl-xL chinese giant salamander iridovirus mitochondria apoptosis Bak p53 |
| title | 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_short | 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 |
| topic | Bcl-xL chinese giant salamander iridovirus mitochondria apoptosis Bak p53 |
| url | https://www.mdpi.com/1999-4915/13/11/2224 |
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