细胞焦亡在肠道病毒A71型感染中的作用

Pyroptosis Supports Enterovirus A71 Infection

肠道病毒A组71型(Enterovirus A71,EV-A71)是引起手足口病(Hand,foot,and mouth disease,HFMD)最常见的病原体之一,而细胞焦亡是一种以细胞溶解及炎症反应为主要特征的细胞程序性死亡。目前细胞焦亡参与EV-A71致病的分子机制尚不清楚。本研究旨在探索EV-A71感染引起的焦亡与病毒感染之间的关系。EV-A71感染Vero细胞,6 h后检测caspase-1 mRNA和蛋白的表达水平,结果显示EV-A71感染促使caspase-1表达升高,表明EV-A71感染引起细胞焦亡;检测IL-1β和IL-18 mRNA和蛋白的表达水平,结果显示EV-A71感染促进IL-1β和IL-18的表达升高,表明EV-A71诱导的焦亡与炎症的产生有关。EV-A71感染后加入caspase-1抑制剂Ac-YVADCMK,在感染后6 h检测caspase-1和EV-A71的mRNA和蛋白的表达水平,结果显示加入Ac-YVAD-CMK可降低caspase-1和EV-A71的mRNA及蛋白水平,表明Ac-YVAD-CMK可抑制细胞焦亡和病毒的感染;检测IL-1β和IL-18 mRNA和蛋白的表达水平,结果显示加入Ac-YVAD-CMK可降低IL-1β和IL-18的表达,表明抑制焦亡可抑制炎症反应。本研究得出结论是EV-A71感染可诱导caspase-1介导的细胞焦亡,抑制caspase-1可有效抑制病毒感染。

Enterovirus A71(EV-A71)is the primary causative pathogen of hand,foot,and mouth disease(HFMD).Pyroptosis is a programmed cell death characterized by cell lysis and inflammatory response.The molecular mechanism of pyroptosis in the pathogenesis of EV71 is poorly defined.To explore the relationship between pyroptosis and infection in Vero cells infected by EV-A71,the mRNA and protein expression of caspase-1 were measured 6 h post-infection.EV-A71 infection increased caspase-1 expression,indicating that EV-A71 infection induced pyroptosis.mRNA and protein expression of interleukin(IL)-1βand IL-18 were also measured.EV-A71 infection increased expression of IL-1βand IL-18,indicating that pyroptosis induced by EV-A71 was associated with inflammation.After infected by EV-A71,cells were treated with caspase-1 inhibitor Ac-YVAD-CMK,then the mRNA and protein expression of caspase-1 and virus were detected 6 h post-infection.Ac-YVAD-CMK treatment decreased expression of caspase-1 and EV-A71,suggesting that AcYVAD-CMK could repress the pyroptosis and viral infection.Then,the mRNA and protein expression of IL-1βand IL-18 were measured.Ac-YVAD-CMK treatment could alleviate inflammatory response,suggesting that inhibition of pyroptosis could decrease inflammation.Hence,EV-A71 infection activated pyroptosis,and inhibition of pyroptosis could reduce EV-A71 infection.