Pyroptosis induced by enterovirus 71 and coxsackievirus B3 infection affects viral replication and host response

• Published in: Scientific reports Vol. 8; no. 1; pp. 2887 - 12
• Main Authors: Wang, Yan, Qin, Ying, Wang, Tianying, Chen, Yang, Lang, Xiujuan, Zheng, Jia, Gao, Shuoyang, Chen, Sijia, Zhong, Xiaoyan, Mu, Yusong, Wu, Xiaoyu, Zhang, Fengming, Zhao, Wenran, Zhong, Zhaohua
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 13.02.2018; Nature Publishing Group UK
• Subjects: Apoptosis; Caspase; Caspase-1; Cell death; Children; Coxsackieviruses; Enterovirus; Hand-foot-and-mouth disease; Infections; Inflammation; Interleukin 18; Lysis; Neurological complications; Pathogenesis; Pyroptosis; Replication
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-20958-1

Enterovirus 71 (EV71) is the primary causative pathogen of hand, foot, and mouth disease (HFMD), affecting children with severe neurological complications. Pyroptosis is a programmed cell death characterized by cell lysis and inflammatory response. Although proinflammatory response has been implicated to play important roles in EV71-caused diseases, the involvement of pyroptosis in the pathogenesis of EV71 is poorly defined. We show that EV71 infection induced caspase-1 activation. Responding to the activation of caspase-1, the expression and secretion of both IL-1β and IL-18 were increased in EV71-infected cells. The treatment of caspase-1 inhibitor markedly improved the systemic response of the EV71-infected mice. Importantly, caspase-1 inhibitor suppressed EV71 replication in mouse brains. Similarly, pyroptosis was activated by the infection of coxsackievirus B3 (CVB3), an important member of the Enterovirus genus. Caspase-1 activation and the increased expression of IL-18 and NLRP3 were demonstrated in HeLa cells infected with CVB3. Caspase-1 inhibitor also alleviated the overall conditions of virus-infected mice with markedly decreased replication of CVB3 and reduced expression of caspase-1. These results indicate that pyroptosis is involved in the pathogenesis of both EV71 and CVB3 infections, and the treatment of caspase-1 inhibitor is beneficial to the host response during enterovirus infection.