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SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation.
Li, Shufen; Zhang, Yulan; Guan, Zhenqiong; Li, Huiling; Ye, Meidi; Chen, Xi; Shen, Jun; Zhou, Yiwu; Shi, Zheng-Li; Zhou, Peng; Peng, Ke.
  • Li S; State Key Laboratory of Virology, CAS Key Laboratory of Special Pathogens, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
  • Zhang Y; State Key Laboratory of Virology, CAS Key Laboratory of Special Pathogens, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
  • Guan Z; State Key Laboratory of Virology, CAS Key Laboratory of Special Pathogens, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
  • Li H; University of Chinese Academy of Sciences, Beijing, China.
  • Ye M; State Key Laboratory of Virology, CAS Key Laboratory of Special Pathogens, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
  • Chen X; University of Chinese Academy of Sciences, Beijing, China.
  • Shen J; State Key Laboratory of Virology, CAS Key Laboratory of Special Pathogens, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
  • Zhou Y; University of Chinese Academy of Sciences, Beijing, China.
  • Shi ZL; Department of Thoracic and Vascular Surgery, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Zhou P; Infectious Disease Department, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China.
  • Peng K; Department of Forensic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Hangkong Road, Wuhan, 430074, China.
Signal Transduct Target Ther ; 5(1): 235, 2020 10 09.
Article in English | MEDLINE | ID: covidwho-841900
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to respiratory illness and multi-organ failure in critically ill patients. Although the virus-induced lung damage and inflammatory cytokine storm are believed to be directly associated with coronavirus disease 2019 (COVID-19) clinical manifestations, the underlying mechanisms of virus-triggered inflammatory responses are currently unknown. Here we report that SARS-CoV-2 infection activates caspase-8 to trigger cell apoptosis and inflammatory cytokine processing in the lung epithelial cells. The processed inflammatory cytokines are released through the virus-induced necroptosis pathway. Virus-induced apoptosis, necroptosis, and inflammation activation were also observed in the lung sections of SARS-CoV-2-infected HFH4-hACE2 transgenic mouse model, a valid model for studying SARS-CoV-2 pathogenesis. Furthermore, analysis of the postmortem lung sections of fatal COVID-19 patients revealed not only apoptosis and necroptosis but also massive inflammatory cell infiltration, necrotic cell debris, and pulmonary interstitial fibrosis, typical of immune pathogenesis in the lung. The SARS-CoV-2 infection triggered a dual mode of cell death pathways and caspase-8-dependent inflammatory responses may lead to the lung damage in the COVID-19 patients. These discoveries might assist the development of therapeutic strategies to treat COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Pulmonary Fibrosis / Apoptosis / Coronavirus Infections / Caspase 8 / Betacoronavirus / Cytokine Release Syndrome / Necroptosis Type of study: Prognostic study Language: English Journal: Signal Transduct Target Ther Year: 2020 Document Type: Article Affiliation country: S41392-020-00334-0

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Pulmonary Fibrosis / Apoptosis / Coronavirus Infections / Caspase 8 / Betacoronavirus / Cytokine Release Syndrome / Necroptosis Type of study: Prognostic study Language: English Journal: Signal Transduct Target Ther Year: 2020 Document Type: Article Affiliation country: S41392-020-00334-0