SFTSV Infection Induces BAK/BAX-Dependent Mitochondrial DNA Release to Trigger NLRP3 Inflammasome Activation - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Accéder directement au contenu
Article Dans Une Revue Cell Reports Année : 2020

SFTSV Infection Induces BAK/BAX-Dependent Mitochondrial DNA Release to Trigger NLRP3 Inflammasome Activation

Shufen Li
  • Fonction : Auteur
Hao Li
Yu-Lan Zhang
  • Fonction : Auteur
Qi-Lin Xin
  • Fonction : Auteur
Zhen-Qiong Guan
  • Fonction : Auteur
Xi Chen
Xiao-Ai Zhang
  • Fonction : Auteur
Xiao-Kun Li
  • Fonction : Auteur
Geng-Fu Xiao
  • Fonction : Auteur
Jun Cui
  • Fonction : Auteur
Wei Liu
Lei-Ke Zhang
  • Fonction : Auteur
Ke Peng

Résumé

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 subsequent cytosolic release. The cytosolic mtDNA binds and triggers NLRP3 inflammasome activation. Notably, the BAK expression level correlates with SFTS disease progression and fatal outcome. These findings provide insights into the clinical features and molecular underpinnings of severe SFTS, which may aid in patient care and therapeutic design, and may also be conserved during infection by other highly pathogenic viruses.
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hal-03154543 , version 1 (07-06-2021)

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Shufen Li, Hao Li, Yu-Lan Zhang, Qi-Lin Xin, Zhen-Qiong Guan, et al.. SFTSV Infection Induces BAK/BAX-Dependent Mitochondrial DNA Release to Trigger NLRP3 Inflammasome Activation. Cell Reports, 2020, 30 (13), pp.4370-4385.e7. ⟨10.1016/j.celrep.2020.02.105⟩. ⟨hal-03154543⟩
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