African Swine Fever Virus pE199L Induces Mitochondrial-Dependent Apoptosis

文献类型： 外文期刊

第一作者： Li, Tingting

作者： Li, Tingting;Zhao, Gaihong;Zhang, Taoqing;Zhang, Zhaoxia;Chen, Xin;Song, Jie;Wang, Xiao;Li, Jiangnan;Huang, Li;Wen, Lili;Li, Changyao;Zhao, Dongming;He, Xijun;Bu, Zhigao;Zheng, Jun;Weng, Changjiang

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关键词： African swine fever virus; pE199L; mitochondria; apoptosis

期刊名称：VIRUSES-BASEL （ 影响因子：5.818； 五年影响因子：5.811 ）

ISSN：

年卷期： 2021 年 13 卷 11 期

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收录情况： SCI

摘要： 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-L, MCL-1, BCL-W, and BCL-2A1) and competed with BAK for BCL-X-L, 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.

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