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Gasdermin E is required for induction of pyroptosis and severe disease during enterovirus 71 infection.
Dong, Siwen; Shi, Yujin; Dong, Xiaojing; Xiao, Xia; Qi, Jianli; Ren, Lili; Xiang, Zichun; Zhou, Zhuo; Wang, Jianwei; Lei, Xiaobo.
Afiliación
  • Dong S; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, B
  • Shi Y; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, B
  • Dong X; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, B
  • Xiao X; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, B
  • Qi J; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China.
  • Ren L; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, B
  • Xiang Z; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, B
  • Zhou Z; Biomedical Pioneering Innovation Center, Beijing Advanced Innovation Center for Genomics, Peking University Genome Editing Research Center, School of Life Sciences, Peking University, Beijing, China.
  • Wang J; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, B
  • Lei X; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, B
J Biol Chem ; 298(5): 101850, 2022 05.
Article en En | MEDLINE | ID: mdl-35339492
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enterovirus Humano A / Infecciones por Enterovirus / Proteínas Citotóxicas Formadoras de Poros / Piroptosis Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enterovirus Humano A / Infecciones por Enterovirus / Proteínas Citotóxicas Formadoras de Poros / Piroptosis Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos