Seneca Valley Virus 2C and 3Cpro Induce Apoptosis via Mitochondrion-Mediated Intrinsic Pathway

被引：45
作者：
Liu, Tingting [1 ,2 ]
Li, Xiangmin [1 ,2 ,3 ,4 ]
Wu, Mengge [1 ,2 ]
Qin, Liuxing [1 ,2 ]
Chen, Huanchun [1 ,2 ,3 ,4 ]
Qian, Ping [1 ,2 ,3 ,4 ]
机构：
[1] Huazhong Agr Univ, Coll Vet Med, State Key Lab Agr Microbiol, Wuhan, Hubei, Peoples R China
[2] Huazhong Agr Univ, Coll Vet Med, Lab Anim Virol, Wuhan, Hubei, Peoples R China
[3] Minist Agr, Key Lab Dev Vet Diagnost Prod, Wuhan, Hubei, Peoples R China
[4] Cooperat Innovat Ctr Sustainable Pig Prod, Key Lab Prevent Vet Med Hubei Prov, Wuhan, Hubei, Peoples R China
来源：
FRONTIERS IN MICROBIOLOGY | 2019年 / 10卷
基金：
中国国家自然科学基金;
关键词：
seneca valley virus (SVV); 2C; 3C(p)(ro); apoptosis; caspase-3; FAMILY; BAX; MECHANISMS; CLEAVAGE; BINDING; PROTEIN; CHINA; SWINE;
D O I：
10.3389/fmicb.2019.01202
中图分类号：
Q93 [微生物学];
学科分类号：
071005 ; 100705 ;
摘要：
Seneca Valley virus (SVV) is the only member of the genus Senecavirus of the Picornaviridae family. SVV can selectively infect and lyse tumor cells with neuroendocrine features and is used as an oncolytic virus for treating small-cell lung cancers. However, the detailed mechanism underlying SVV-mediated destruction of tumor cells remains unclear. In this study, we found that SVV can increase the proportion of apoptotic 293T cells in a dose- and time-dependent manner. SVV-induced apoptosis was initiated via extrinsic and intrinsic pathways through activation of caspase-3, the activity of which could be attenuated by a pan-caspase inhibitor (Z-VAD-FMK). We confirmed that SVV 2C and 3C(pro) play critical roles in SVV-induced apoptosis. The SVV 2C protein was located solely in the mitochondria and activated caspase-3 to induce apoptosis. SVV 3C(pro) induced apoptosis through its protease activity, which was accompanied by release of cytochrome C into the cytoplasm, but did not directly cleave PARP1.
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页数：12
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