We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
H7N9 virus infection triggers lethal cytokine storm by activating gasdermin E-mediated pyroptosis of lung alveolar epithelial cells.
- Authors
Wan, Xiaopeng; Li, Jiqing; Wang, Yupeng; Yu, Xiaofei; He, Xijun; Shi, Jianzhong; Deng, Guohua; Zeng, Xianying; Tian, Guobin; Li, Yanbing; Jiang, Yongping; Guan, Yuntao; Li, Chengjun; Shao, Feng; Chen, Hualan
- Abstract
The H7N9 influenza virus emerged in China in 2013, causing more than 1560 human infections, 39% of which were fatal. A 'cytokine storm' in the lungs of H7N9 patients has been linked to a poor prognosis and death; however, the underlying mechanism that triggers the cytokine storm is unknown. Here, we found that efficient replication of the H7N9 virus in mouse lungs activates gasdermin E (GSDME)-mediated pyroptosis in alveolar epithelial cells, and that the released cytosolic contents then trigger a cytokine storm. Knockout of Gsdme switched the manner of death of A549 and human primary alveolar epithelial cells from pyroptosis to apoptosis upon H7N9 virus infection, and Gsdme knockout mice survived H7N9 virus lethal infection. Our findings reveal that GSDME activation is a key and unique mechanism for the pulmonary cytokine storm and lethal outcome of H7N9 virus infection and thus opens a new door for the development of antivirals against the H7N9 virus.
- Subjects
CHINA; INFLUENZA A virus, H7N9 subtype; CYTOKINE release syndrome; LUNGS; EPITHELIAL cells; PYROPTOSIS; KNOCKOUT mice; VIRUS diseases
- Publication
National Science Review, 2022, Vol 9, Issue 1, p1
- ISSN
2095-5138
- Publication type
Article
- DOI
10.1093/nsr/nwab137