Caspase-3 Inhibition Attenuates the Cytopathic Effects of EV71 Infection

• Published in: Frontiers in microbiology Vol. 9; p. 817
• Main Authors: Song, Fengmei, Yu, Xiaoyan, Zhong, Ting, Wang, Zengyan, Meng, Xiangling, Li, Zhaolong, Zhang, Shuxia, Huo, Wenbo, Liu, Xin, Zhang, Yahong, Zhang, Wenyan, Yu, Jinghua
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 26-04-2018
• Subjects: caspase-3; EV71; host–pathogen interaction; Microbiology; non-structural protein 3C; viral production; EV71; non-structural protein 3C; viral production; host–pathogen interaction; caspase-3
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2018.00817

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.