SFTSV Infection Induces BAK/BAX-Dependent Mitochondrial DNA Release to Trigger NLRP3 Inflammasome Activation
作者: Shufen LiHao LiYu-Lan ZhangQi-Lin XinZhen-Qiong GuanXi ChenXiao-Ai ZhangXiao-Kun LiGeng-Fu XiaoPierre-Yves LozachJun CuiWei LiuLei-Ke ZhangKe Peng
作者单位: 1State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei 430071, P. R. China
2State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing Key Laboratory of Vector Borne and Natural Focus Infectious Diseases, Beijing 100071, P. R. China
3University of the Chinese Academy of Sciences, Beijing 100049, P. R. China
4Department of Thoracic and Vascular Surgery, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P. R. China
5Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany
6IVPC UMR754, INRA, University of Lyon, EPHE, 50 Av. Tony Garnier, 69007 Lyon, France
7MOE Key Laboratory of Gene Function and Regulation, State Key Lab of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China
刊名: Cell Reports, 2020, Vol.30 (13), pp.4370-4385.e7
来源数据库: Elsevier Journal
DOI: 10.1016/j.celrep.2020.02.105
关键词: SFTSVMitochondrial DNANLRP3 inflammasomeBAKBAX
原始语种摘要: Summary(#br)Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus that carries a high fatality rate of 12%–50%. In-depth understanding of the SFTSV-induced pathogenesis mechanism is critical for developing effective anti-SFTS therapeutics. Here, we report transcriptomic analysis of blood samples from SFTS patients. We observe a strong correlation between inflammatory responses and disease progression and fatal outcome. Quantitative proteomic analysis of SFTSV infection confirms the induction of inflammation and further reveals virus-induced mitochondrial dysfunction. Mechanistically, SFTSV infection triggers BCL2 antagonist/killer 1 (BAK) upregulation and BAK/BCL2-associated X (BAX) activation, leading to mitochondrial DNA (mtDNA) oxidization and...
全文获取路径: Elsevier  (合作)

  • therapeutics 治疗学
  • induced 感应的
  • fatality 致死率
  • activation 活化
  • developing 显影
  • infection 感染
  • Release 免除释放机构
  • mitochondrial 线粒体的
  • inflammation 炎症
  • virus 病毒