The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice

Linlin Bao, Wei Deng, Baoying Huang, Hong Gao, Jiangning Liu, Lili Ren, Qiang Wei, Pin Yu, Yanfeng Xu, Feifei Qi, Yajin Qu, Fengdi Li, Qi Lv, Wenling Wang, Jing Xue, Shuran Gong, Mingya Liu, Guanpeng Wang, Shunyi Wang, Zhiqi Song, Linna Zhao, Peipei Liu, Li Zhao, Fei Ye, Huijuan Wang, Weimin Zhou, Na Zhu, Wei Zhen, Haisheng Yu, Xiaojuan Zhang, Li Guo, Lan Chen, Conghui Wang, Ying Wang, Xinming Wang, Yan Xiao, Qiangming Sun, Hongqi Liu, Fanli Zhu, Chunxia Ma, Lingmei Yan, Mengli Yang, Jun Han, Wenbo Xu, Wenjie Tan, Xiaozhong Peng, Qi Jin, Guizhen Wu () and Chuan Qin ()
Additional contact information
Linlin Bao: Chinese Academy of Medical Sciences
Wei Deng: Chinese Academy of Medical Sciences
Baoying Huang: National Institute for Viral Disease Control and Prevention, China CDC
Hong Gao: Chinese Academy of Medical Sciences
Jiangning Liu: Chinese Academy of Medical Sciences
Lili Ren: Chinese Academy of Medical Sciences
Qiang Wei: Chinese Academy of Medical Sciences
Pin Yu: Chinese Academy of Medical Sciences
Yanfeng Xu: Chinese Academy of Medical Sciences
Feifei Qi: Chinese Academy of Medical Sciences
Yajin Qu: Chinese Academy of Medical Sciences
Fengdi Li: Chinese Academy of Medical Sciences
Qi Lv: Chinese Academy of Medical Sciences
Wenling Wang: National Institute for Viral Disease Control and Prevention, China CDC
Jing Xue: Chinese Academy of Medical Sciences
Shuran Gong: Chinese Academy of Medical Sciences
Mingya Liu: Chinese Academy of Medical Sciences
Guanpeng Wang: Chinese Academy of Medical Sciences
Shunyi Wang: Chinese Academy of Medical Sciences
Zhiqi Song: Chinese Academy of Medical Sciences
Linna Zhao: Chinese Academy of Medical Sciences
Peipei Liu: National Institute for Viral Disease Control and Prevention, China CDC
Li Zhao: National Institute for Viral Disease Control and Prevention, China CDC
Fei Ye: National Institute for Viral Disease Control and Prevention, China CDC
Huijuan Wang: National Institute for Viral Disease Control and Prevention, China CDC
Weimin Zhou: National Institute for Viral Disease Control and Prevention, China CDC
Na Zhu: National Institute for Viral Disease Control and Prevention, China CDC
Wei Zhen: National Institute for Viral Disease Control and Prevention, China CDC
Haisheng Yu: Chinese Academy of Medical Sciences
Xiaojuan Zhang: Chinese Academy of Medical Sciences
Li Guo: Chinese Academy of Medical Sciences
Lan Chen: Chinese Academy of Medical Sciences
Conghui Wang: Chinese Academy of Medical Sciences
Ying Wang: Chinese Academy of Medical Sciences
Xinming Wang: Chinese Academy of Medical Sciences
Yan Xiao: Chinese Academy of Medical Sciences
Qiangming Sun: Chinese Academy of Medical Sciences
Hongqi Liu: Chinese Academy of Medical Sciences
Fanli Zhu: Chinese Academy of Medical Sciences
Chunxia Ma: Chinese Academy of Medical Sciences
Lingmei Yan: Chinese Academy of Medical Sciences
Mengli Yang: Chinese Academy of Medical Sciences
Jun Han: National Institute for Viral Disease Control and Prevention, China CDC
Wenbo Xu: National Institute for Viral Disease Control and Prevention, China CDC
Wenjie Tan: National Institute for Viral Disease Control and Prevention, China CDC
Xiaozhong Peng: Chinese Academy of Medical Sciences
Qi Jin: Chinese Academy of Medical Sciences
Guizhen Wu: National Institute for Viral Disease Control and Prevention, China CDC
Chuan Qin: Chinese Academy of Medical Sciences

Nature, 2020, vol. 583, issue 7818, 830-833

Abstract: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern1. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)2. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.

Date: 2020
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DOI: 10.1038/s41586-020-2312-y

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