Caspase-3 inhibitor inhibits enterovirus D68 production
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Caspase-3 inhibitor inhibits enterovirus D68 production Wenbo Huo1,2Ъ, Jinghua Yu1Ъ, Chunyu Liu3, Ting Wu4, Yue Wang5, Xiangling Meng2, Fengmei Song2, Shuxia Zhang2, Ying Su2, Yumeng Liu2, Jinming Liu2, Xiaoyan Yu2, and Shucheng Hua6* 1
Institute of Virology and AIDS Research, The First Hospital of Jilin University, Jilin University, Changchun 130000, P. R. China Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Science, Jilin University, Changhun 130000, P. R. China 3 Acupuncture Department, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130000, P. R. China 4 Neonatal Intensive Care Unit, The First Hospital of Jilin University, Jilin University, Changchun 130000, P. R. China 5 Department of Chemistry of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130000, P. R. China 6 Department of Internal Medicine, The First Hospital of Jilin University, Jilin University, Changchun 130000, P. R. China 2
(Received May 8, 2020 / Revised Jun 19, 2020 / Accepted Jun 22, 2020)
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-DEVDFMK) 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 Introduction Human enterovirus 68 (EVD68) was originally isolated in California in 1962 from four children with respiratory illness. Since that time, reports of EVD68 infection have been scarce; however, over the past 10 years, EVD68 infection outbreaks have been reported in Italy, the United States, Germany, China, and several other countries (Esposito et al., 2015; Far† These authors contributed equally to this work. *For correspondence. E-mail: [email protected]; Tel./Fax: +86-4318783235 Copyright G2020, The Microbiological Society of Korea
rell et al., 2015; Reiche et al., 2015; Zhang et al., 2015; Carballo et al., 2019; Kamau et al., 2019; Messacar and Tyler, 2019), with a record number of confirmed cases in 2014 (http:// www.cdc.gov/non-polio-enterovirus/about/ev-d68.html). EVD68 is associated with respiratory illness, neurological complications, and even death among children. Unfortunately, there are still no available vaccines or medicines, which may be largely because the pathogenic mechanism of EVD68 has not been well explained. EVD68
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