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

Tingting Liu; Xiangmin Li; Mengge Wu; Liuxing Qin; Huanchun Chen; Ping Qian

doi:10.3389/fmicb.2019.01202

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

Front Microbiol. 2019 May 29:10:1202. doi: 10.3389/fmicb.2019.01202. eCollection 2019.

Authors

Tingting Liu^{1

2}, Xiangmin Li^{1

2

3

4}, Mengge Wu^{1

2}, Liuxing Qin^{1

2}, Huanchun Chen^{1

2

3

4}, Ping Qian^{1

2

3

4}

Affiliations

¹ State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.
² Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
³ Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Wuhan, China.
⁴ Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.

Abstract

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.

Keywords: 2C; 3Cpro; apoptosis; caspase-3; seneca valley virus (SVV).