| Title | Gasdermin E is required for induction of pyroptosis and severe disease during enterovirus 71 infection |
| Authors | Dong, Siwen Shi, Yujin Dong, Xiaojing Xiao, Xia Qi, Jianli Ren, Lili Xiang, Zichun Zhou, Zhuo Wang, Jianwei Lei, Xiaobo |
| Affiliation | Chinese Acad Med Sci & Peking Union Med Coll, Inst Pathogen Biol, NHC Key Lab Syst Biol Pathogens, Beijing, Peoples R China Chinese Acad Med Sci & Peking Union Med Coll, Key Lab Resp Dis Pathogen, Beijing, Peoples R China Peking Univ, Genome Editing Res Ctr, Biomed Pioneering Innovat Ctr, Beijing Adv Innovat Ctr Genom,Sch Life Sci, Beijing, Peoples R China |
| Keywords | MOUTH-DISEASE INFLAMMATORY CASPASES CLINICAL-FEATURES CELL-DEATH HAND FOOT ACTIVATION APOPTOSIS CHILDREN PROTEIN |
| Issue Date | May-2022 |
| Publisher | JOURNAL OF BIOLOGICAL CHEMISTRY |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/670158 |
| DOI | 10.1016/j.jbc.2022.101850 |
| Indexed | SCI(E) |
| Appears in Collections: | 生命科学学院 |
