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. 2020 Jul;583(7818):830-833.
doi: 10.1038/s41586-020-2312-y. Epub 2020 May 7.

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

Linlin Bao #  1   2 , Wei Deng #  1   2 , Baoying Huang #  3 , Hong Gao #  1   2 , Jiangning Liu #  1   2 , Lili Ren  4 , Qiang Wei  1   2 , Pin Yu  1   2 , Yanfeng Xu  1   2 , Feifei Qi  1   2 , Yajin Qu  1   2 , Fengdi Li  1   2 , Qi Lv  1   2 , Wenling Wang  3 , Jing Xue  1   2 , Shuran Gong  1   2 , Mingya Liu  1   2 , Guanpeng Wang  1   2 , Shunyi Wang  1   2 , Zhiqi Song  1   2 , Linna Zhao  1   2 , Peipei Liu  3 , Li Zhao  3 , Fei Ye  3 , Huijuan Wang  3 , Weimin Zhou  3 , Na Zhu  3 , Wei Zhen  3 , Haisheng Yu  1   2 , Xiaojuan Zhang  1   2 , Li Guo  4 , Lan Chen  4 , Conghui Wang  4 , Ying Wang  4 , Xinming Wang  4 , Yan Xiao  4 , Qiangming Sun  5 , Hongqi Liu  5 , Fanli Zhu  5 , Chunxia Ma  5 , Lingmei Yan  5 , Mengli Yang  5 , Jun Han  3 , Wenbo Xu  3 , Wenjie Tan  3 , Xiaozhong Peng  5 , Qi Jin  4 , Guizhen Wu  6 , Chuan Qin  7   8
Affiliations

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

Linlin Bao et al. Nature. 2020 Jul.

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.

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