Reciprocal Regulation between Enterovirus 71 and the NLRP3 Inflammasome
Reciprocal Regulation between Enterovirus 71 and the NLRP3 Inflammasome
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肠道病毒 71 和 NLRP3 炎症体之间的相互调节。
DOI：
10.1016/j.celrep.2015.05.047
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发表时间：
2015-07-07
期刊：
影响因子：
8.8
通讯作者：
Wang, Jianwei
中科院分区：
文献类型：
--
作者：
Wang, Hongbin;Lei, Xiaobo;Wang, Jianwei
肠道病毒71型(EV71)是手足口病的主要病原。早期研究表明，有严重并发症的EV71感染患者血浆IL-1β水平升高，表明EV71可能激活了炎性小体。我们目前的研究表明，NLRP3炎症体对小鼠体内感染EV71具有保护作用。EV71在髓系细胞中的复制导致NLRP3炎症体的激活和IL-1b的分泌。相反，EV71通过病毒蛋白水解酶2A和3C裂解NLRP3来中和炎症体的激活，这两种酶分别在G493-L494或Q225-G226连接处裂解NLRP3蛋白。此外，EV71 3C与NLRP3相互作用，在哺乳动物细胞中表达时抑制IL-1b的分泌。因此，这些结果揭示了肠道病毒71和NLRP3炎症体之间的一套相互调节。
Enterovirus 71 (EV71) is the major etiological agent of hand, foot, and mouth disease (HFMD). Early studies showed that EV71-infected patients with severe complications exhibited elevated plasma levels of IL-1 beta, indicating that EV71 may activate inflammasomes. Our current study demonstrates that the NLRP3 inflammasome plays a protective role against EV71 infection of mice in vivo. EV71 replication in myeloid cells results in the activation of the NLRP3 inflammasome and secretion of IL-1b. Conversely, EV71 counteracts inflammasome activation through cleavage of NLRP3 by viral proteases 2A and 3C, which cleave NLRP3 protein at the G493-L494 or Q225-G226 junction, respectively. Moreover, EV71 3C interacts with NLRP3 and inhibits IL-1b secretion when expressed in mammalian cells. These results thus reveal a set of reciprocal regulations between enterovirus 71 and the NLRP3 inflammasome.