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Gasdermin E is required for induction of pyroptosis and severe disease during enterovirus 71 infection

The Journal of biological chemistry, 2022-05, Vol.298 (5), p.101850-101850, Article 101850 [Peer Reviewed Journal]

2022 The Authors ;Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. ;2022 The Authors 2022 ;ISSN: 0021-9258 ;EISSN: 1083-351X ;DOI: 10.1016/j.jbc.2022.101850 ;PMID: 35339492

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  • Title:
    Gasdermin E is required for induction of pyroptosis and severe disease during enterovirus 71 infection
  • Author: Dong, Siwen ; Shi, Yujin ; Dong, Xiaojing ; Xiao, Xia ; Qi, Jianli ; Ren, Lili ; Xiang, Zichun ; Zhou, Zhuo ; Wang, Jianwei ; Lei, Xiaobo
  • Subjects: caspase-3 ; EV71 ; GSDME ; pyroptosis
  • Is Part Of: The Journal of biological chemistry, 2022-05, Vol.298 (5), p.101850-101850, Article 101850
  • Description: 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.
  • Publisher: United States: Elsevier Inc
  • Language: English
  • Identifier: ISSN: 0021-9258
    EISSN: 1083-351X
    DOI: 10.1016/j.jbc.2022.101850
    PMID: 35339492
  • Source: PubMed Central
    Alma/SFX Local Collection
    DOAJ Directory of Open Access Journals
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