(Peer-Reviewed) H7N9 virus infection triggers lethal cytokine storm by activating gasdermin E-mediated pyroptosis of lung alveolar epithelial cells
Xiaopeng Wan ¹, Jiqing Li ¹, Yupeng Wang ², Xiaofei Yu ¹, Xijun He ¹, Jianzhong Shi 施建忠 ¹, Guohua Deng 邓国华 ¹, Xianying Zeng 曾显营 ¹, Guobin Tian 田国彬 ¹, Yanbing Li 李雁冰 ¹, Yongping Jiang 姜永萍 ¹, Yuntao Guan ¹, Chengjun Li 李呈军 ¹, Feng Shao 邵峰 ², Hualan Chen 陈化兰 ¹
¹ State Key Laboratory Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Science, Harbin 150001, China. 中国农业科学院 哈尔滨兽医研究所 兽医生物技术国家重点实验室
² National Institute of Biological Sciences, Beijing 102206, China 北京生命科学研究所
National Science Review
, 2021-07-30
Abstract
The H7N9 influenza virus emerged in China in 2013, causing more than 1,560 human infections, 39% of which were fatal. A ‘cytokine storm’ in 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 H7N9 virus in mouse lung 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 death manner 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 H7N9 virus.
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