Gasdermin E is required for induction of pyroptosis and severe disease during enterovirus 71 infection.
Gasdermin E is required for induction of pyroptosis and severe disease during enterovirus 71 infection.
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DOI：
10.1016/j.jbc.2022.101850
复制
发表时间：
2022-05
影响因子：
4.8
通讯作者：
Lei, Xiaobo
中科院分区：
文献类型：
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作者：
Dong, Siwen;Shi, Yujin;Dong, Xiaojing;Xiao, Xia;Qi, Jianli;Ren, Lili;Xiang, Zichun;Zhou, Zhuo;Wang, Jianwei;Lei, Xiaobo
焦亡是程序性细胞死亡的炎性形式，其由GSDM家族蛋白的gasdermin（GSDM）-N结构域执行，其在质膜中形成孔。虽然焦亡作为宿主防御侵入性病原体感染，其在肠道病毒71（EV 71）感染的发病机制中的作用尚不清楚。在目前的研究中，我们发现，EV 71感染诱导GSDM E（GSDME）的裂解，通过使用蛋白质印迹分析，在开关从caspase-3介导的细胞凋亡到pyroptosis的一个重要步骤。我们表明，这种切割是独立的3C和2A蛋白酶的EV 71。然而，半胱天冬酶-3活化对于这种切割是必需的，因为在EV 71感染后，GSDME不能在半胱天冬酶-3-KO细胞中被切割。进一步分析显示，EV 71感染在WT细胞中诱导了焦亡，但在caspase-3/GSDME双KO细胞中没有。重要的是，在EV 71感染期间，需要GSDME来诱导严重的疾病，因为小鼠中的GSDME缺乏显示出减轻病理症状。总之，我们的研究结果表明，GSDME是重要的发病机制，EV 71通过介导的启动pyroptosis。
Pyroptosis is an inflammatory form of programmed cell death that is executed by the gasdermin (GSDM)-N domain of GSDM family proteins, which form pores in the plasma membrane. Although pyroptosis acts as a host defense against invasive pathogen infection, its role in the pathogenesis of enterovirus 71 (EV71) infection is unclear. In the current study, we found that EV71 infection induces cleavage of GSDM E (GSDME) by using western blotting analysis, an essential step in the switch from caspase-3-mediated apoptosis to pyroptosis. We show that this cleavage is independent of the 3C and 2A proteases of EV71. However, caspase-3 activation is essential for this cleavage, as GSDME could not be cleaved in caspase-3-KO cells upon EV71 infection. Further analyses showed that EV71 infection induced pyroptosis in WT cells but not in caspase-3/GSDME double-KO cells. Importantly, GSDME is required to induce severe disease during EV71 infection, as GSDME deficiency in mice was shown to alleviate pathological symptoms. In conclusion, our results reveal that GSDME is important for the pathogenesis of EV71 via mediating initiation of pyroptosis.
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高尔基体蛋白 ACBD3 通过与 3A 相互作用促进肠道病毒 71 复制。
影响因子：
4.6
作者：
Lei X;Xiao X;Zhang Z;Ma Y;Qi J;Wu C;Xiao Y;Zhou Z;He B;Wang J
通讯作者：
Wang J
DOI：
10.1073/pnas.1607769113
发表时间：
2016-07-12
影响因子：
11.1
作者：
Aglietti, Robin A.;Estevez, Alberto;Dueber, Erin C.
通讯作者：
Dueber, Erin C.
肠道病毒71诱导细胞死亡的特征和基因组扫描以确定参与病毒诱导细胞凋亡的病毒基因
影响因子：
5
作者：
Bai, Jinjin;Chen, Xixi;Long, Jian-Er
通讯作者：
Long, Jian-Er
影响因子：
64.8
作者：
Ding, Jingjin;Wang, Kun;Shao, Feng
通讯作者：
Shao, Feng
焦亡是由非选择性gasdermin-D孔驱动的，其形态与MLKL通道介导的坏死性凋亡不同
影响因子：
44.1
作者：
通讯作者：
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