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

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 implicat...

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Published in:Scientific reports 2018-02, Vol.8 (1), p.2887-12, Article 2887
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
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Language:English
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-20958-1