African Swine Fever Virus pE199L Induces Mitochondrial-Dependent Apoptosis

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

doi:10.3390/v13112240

Viruses (Nov 2021)

African Swine Fever Virus pE199L Induces Mitochondrial-Dependent Apoptosis

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

Affiliations

Tingting Li: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Gaihong Zhao: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Taoqing Zhang: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Zhaoxia Zhang: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Xin Chen: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Jie Song: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Xiao Wang: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Jiangnan Li: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Li Huang: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Lili Wen: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Changyao Li: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Dongming Zhao: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Xijun He: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Zhigao Bu: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Jun Zheng: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Changjiang Weng: Division of Fundamental Immunology, National African Swine Fever Para-Reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China

DOI: https://doi.org/10.3390/v13112240
Journal volume & issue: Vol. 13, no. 11
p. 2240

Abstract

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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-XL, MCL-1, BCL-W, and BCL-2A1) and competed with BAK for BCL-XL, 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.

Published in Viruses

ISSN: 1999-4915 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.mdpi.com/journal/viruses

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