SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation
Autor
Li, Shufen
Zhang, Yulan
Guan, Zhenqiong
Li, Huiling
Ye, Meidi
Chen, Xi
Shen, Jun
Zhou, Yiwu
Shi, Zheng-Li
Zhou1, Peng
Peng, Ke
Institución
Resumen
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.