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. 2020 Sep 1;58(9):812–820. doi: 10.1007/s12275-020-0241-y

Caspase-3 inhibitor inhibits enterovirus D68 production

Wenbo Huo 1,2,#, Jinghua Yu 1,#, Chunyu Liu 3, Ting Wu 4, Yue Wang 5, Xiangling Meng 2, Fengmei Song 2, Shuxia Zhang 2, Ying Su 2, Yumeng Liu 2, Jinming Liu 2, Xiaoyan Yu 2, Shucheng Hua 6,✉
PMCID: PMC7459088  PMID: 32870487

Abstract

Enterovirus D68 (EVD68) is an emerging pathogen that recently caused a large worldwide outbreak of severe respiratory disease in children. However, the relationship between EVD68 and host cells remains unclear. Caspases are involved in cell death, immune response, and even viral production. We found that caspase-3 was activated during EVD68 replication to induce apoptosis. Caspase-3 inhibitor (Z-DEVD-FMK) inhibited viral production, protected host cells from the cytopathic effects of EVD68 infection, and prevented EVD68 from regulating the host cell cycle at G0/G1. Meanwhile, caspase-3 activator (PAC-1) increased EVD68 production. EVD68 infection therefore activates caspase-3 for virus production. This knowledge provides a potential direction for the prevention and treatment of disease related to EVD68.

Keywords: EVD68, caspase-3, apoptosis, viral production, host-pathogen interaction

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81871634 and 81301416), Postdoctoral Science Foundation of China (2014M561302 and 2015-T80299), Norman Bethune Program of Jilin University (2015–202), the Jilin Provincial Science and Technology Department (20140204004YY, 20160414025GH and 20190304064YY), and the Department of Human Resources and Social Security of Jilin Province (2016014).

Footnotes

Conflict of Interest

The authors declare no conflict of interest.

These authors contributed equally to this work.

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