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Front. Microbiol. | doi: 10.3389/fmicb.2019.01202

Seneca Valley virus 2C and 3Cpro induce apoptosis via mitochondrion-mediated intrinsic pathway

Tingting Liu1, Xiangmin Li1, Mengge Wu1, Liuxing Qin1,  Huanchun Chen1 and  Ping Qian2*
  • 1Huazhong Agricultural University, China
  • 2State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, 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 3Cpro 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 3Cpro induced apoptosis through its protease activity, which was accompanied by release of cytochrome C into the cytoplasm, but did not directly cleave PARP1.

Keywords: Seneca Valley virus (SVV), 3Cpro, Apoptosis, caspase-3, 2C

Received: 30 Jan 2019; Accepted: 13 May 2019.

Edited by:

Douglas P. Gladue, Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, United States

Reviewed by:

John Zaunders, St Vincent’s Hospital Sydney, Australia
Zixiang2 Zhu, Lanzhou Veterinary Research Institute (CAAS), China  

Copyright: © 2019 Liu, Li, Wu, Qin, Chen and Qian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Ping Qian, State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China, qianp@mail.hzau.edu.cn