Caspase-3 Inhibition Attenuates the Cytopathic Effects of EV71 Infection
Previous studies demonstrate that human enterovirus 71 (EV71), a primary causative agent for hand, foot, and mouth disease, activates caspase-3 through the non-structural viral 3C protein to induce host cell apoptosis; however, until now it was unclear how 3C activates caspase-3 and how caspase-3 ac...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00817/full |
| _version_ | 1811225225998630912 |
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| author | Fengmei Song Fengmei Song Xiaoyan Yu Ting Zhong Zengyan Wang Xiangling Meng Zhaolong Li Shuxia Zhang Wenbo Huo Xin Liu Yahong Zhang Wenyan Zhang Jinghua Yu |
| author_facet | Fengmei Song Fengmei Song Xiaoyan Yu Ting Zhong Zengyan Wang Xiangling Meng Zhaolong Li Shuxia Zhang Wenbo Huo Xin Liu Yahong Zhang Wenyan Zhang Jinghua Yu |
| author_sort | Fengmei Song |
| collection | DOAJ |
| description | Previous studies demonstrate that human enterovirus 71 (EV71), a primary causative agent for hand, foot, and mouth disease, activates caspase-3 through the non-structural viral 3C protein to induce host cell apoptosis; however, until now it was unclear how 3C activates caspase-3 and how caspase-3 activation affects viral production. Our results demonstrate that 3C binds caspase-8 and caspase-9 but does not directly bind caspase-3 to activate them, and that the proteolytic activity of 3C is required by the activation of caspase-8, caspase-9, and caspase-3. Inhibition of caspase-3 activity attenuates apoptosis in 3C-transfected cells. Furthermore, caspase-3 inhibitor protects host cells from the cytopathic effect of EV71 infection and prevents cell cycle arrest, which is known to be favored for EV71 viral replication. Inhibition of caspase-3 activity decreases EV71 viral protein expression and viral production, but has no effect on viral entry, replication, even polyprotein translation. Therefore, caspase-3 is exploited functionally by EV71 to facilitate its production, which suggests a novel therapeutic approach for the treatment and prevention of hand, foot, and mouth disease. |
| first_indexed | 2024-04-12T09:03:32Z |
| format | Article |
| id | doaj.art-211897c24f08472c821ebdc33de9e7f4 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-12T09:03:32Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-211897c24f08472c821ebdc33de9e7f42022-12-22T03:39:10ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-04-01910.3389/fmicb.2018.00817331137Caspase-3 Inhibition Attenuates the Cytopathic Effects of EV71 InfectionFengmei Song0Fengmei Song1Xiaoyan Yu2Ting Zhong3Zengyan Wang4Xiangling Meng5Zhaolong Li6Shuxia Zhang7Wenbo Huo8Xin Liu9Yahong Zhang10Wenyan Zhang11Jinghua Yu12Institute of Virology and AIDS Research, The First Hospital of Jilin University, Jilin University, Changchun, ChinaDepartment of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, ChinaDepartment of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, ChinaCollege of Pharmacy, Central South University, Changsha, ChinaDepartment of Internal Medicine, The First Hospital of Jilin University, Jilin University, Changchun, ChinaDepartment of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, ChinaInstitute of Virology and AIDS Research, The First Hospital of Jilin University, Jilin University, Changchun, ChinaDepartment of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, ChinaDepartment of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, ChinaInstitute of Virology and AIDS Research, The First Hospital of Jilin University, Jilin University, Changchun, ChinaKey Laboratory of Natural Medicines and Immunotechnology of Henan Province, Henan University, Kaifeng, ChinaInstitute of Virology and AIDS Research, The First Hospital of Jilin University, Jilin University, Changchun, ChinaInstitute of Virology and AIDS Research, The First Hospital of Jilin University, Jilin University, Changchun, ChinaPrevious studies demonstrate that human enterovirus 71 (EV71), a primary causative agent for hand, foot, and mouth disease, activates caspase-3 through the non-structural viral 3C protein to induce host cell apoptosis; however, until now it was unclear how 3C activates caspase-3 and how caspase-3 activation affects viral production. Our results demonstrate that 3C binds caspase-8 and caspase-9 but does not directly bind caspase-3 to activate them, and that the proteolytic activity of 3C is required by the activation of caspase-8, caspase-9, and caspase-3. Inhibition of caspase-3 activity attenuates apoptosis in 3C-transfected cells. Furthermore, caspase-3 inhibitor protects host cells from the cytopathic effect of EV71 infection and prevents cell cycle arrest, which is known to be favored for EV71 viral replication. Inhibition of caspase-3 activity decreases EV71 viral protein expression and viral production, but has no effect on viral entry, replication, even polyprotein translation. Therefore, caspase-3 is exploited functionally by EV71 to facilitate its production, which suggests a novel therapeutic approach for the treatment and prevention of hand, foot, and mouth disease.http://journal.frontiersin.org/article/10.3389/fmicb.2018.00817/fullEV71caspase-3viral productionnon-structural protein 3Chost–pathogen interaction |
| spellingShingle | Fengmei Song Fengmei Song Xiaoyan Yu Ting Zhong Zengyan Wang Xiangling Meng Zhaolong Li Shuxia Zhang Wenbo Huo Xin Liu Yahong Zhang Wenyan Zhang Jinghua Yu Caspase-3 Inhibition Attenuates the Cytopathic Effects of EV71 Infection Frontiers in Microbiology EV71 caspase-3 viral production non-structural protein 3C host–pathogen interaction |
| title | Caspase-3 Inhibition Attenuates the Cytopathic Effects of EV71 Infection |
| title_full | Caspase-3 Inhibition Attenuates the Cytopathic Effects of EV71 Infection |
| title_fullStr | Caspase-3 Inhibition Attenuates the Cytopathic Effects of EV71 Infection |
| title_full_unstemmed | Caspase-3 Inhibition Attenuates the Cytopathic Effects of EV71 Infection |
| title_short | Caspase-3 Inhibition Attenuates the Cytopathic Effects of EV71 Infection |
| title_sort | caspase 3 inhibition attenuates the cytopathic effects of ev71 infection |
| topic | EV71 caspase-3 viral production non-structural protein 3C host–pathogen interaction |
| url | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00817/full |
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