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

• Published in: Nature (London) Vol. 583; no. 7818; pp. 830 - 833
• Main Authors: Bao, Linlin, Deng, Wei, Huang, Baoying, Gao, Hong, Liu, Jiangning, Ren, Lili, Wei, Qiang, Yu, Pin, Xu, Yanfeng, Qi, Feifei, Qu, Yajin, Li, Fengdi, Lv, Qi, Wang, Wenling, Xue, Jing, Gong, Shuran, Liu, Mingya, Wang, Guanpeng, Wang, Shunyi, Song, Zhiqi, Zhao, Linna, Liu, Peipei, Zhao, Li, Ye, Fei, Wang, Huijuan, Zhou, Weimin, Zhu, Na, Zhen, Wei, Yu, Haisheng, Zhang, Xiaojuan, Guo, Li, Chen, Lan, Wang, Conghui, Wang, Ying, Wang, Xinming, Xiao, Yan, Sun, Qiangming, Liu, Hongqi, Zhu, Fanli, Ma, Chunxia, Yan, Lingmei, Yang, Mengli, Han, Jun, Xu, Wenbo, Tan, Wenjie, Peng, Xiaozhong, Jin, Qi, Wu, Guizhen, Qin, Chuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.07.2020; Nature Publishing Group
• Subjects: 13/51; 38/77; 631/326/596/2078; 631/326/596/4130; 64/110; 692/420/254; ACE2; Alveoli; Analysis; Angiotensin; Angiotensin converting enzyme; Angiotensin-Converting Enzyme 2; Animals; Antigens; Antigens, Viral - immunology; Antigens, Viral - metabolism; Antiviral drugs; Betacoronavirus - immunology; Betacoronavirus - metabolism; Betacoronavirus - pathogenicity; Bronchi - pathology; Bronchi - virology; Chemical compounds; Coronavirus Infections - immunology; Coronavirus Infections - pathology; Coronavirus Infections - virology; Coronaviruses; COVID-19; Disease Models, Animal; Epithelial cells; Epithelial Cells - pathology; Epithelial Cells - virology; Fatalities; Female; Genetic aspects; Genetically modified mice; Histopathology; Humanities and Social Sciences; Humans; Immunoglobulin G - immunology; Infections; Lung - immunology; Lung - pathology; Lung - virology; Lungs; Lymphocytes; Lymphocytes - immunology; Macrophages; Macrophages, Alveolar - immunology; Macrophages, Alveolar - virology; Male; Mice; Mice, Transgenic; multidisciplinary; Neutrophils; Pandemics; Pathogenesis; Pathogenicity; Pathogens; Peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; Pharmacology; Pneumonia; Pneumonia, Viral - immunology; Pneumonia, Viral - pathology; Pneumonia, Viral - virology; Public health; Receptors, Complement 3d - genetics; Receptors, Complement 3d - metabolism; Respiratory diseases; Rodents; SARS-CoV-2; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Transgenes; Transgenic animals; Transgenic mice; Vaccines; Viral diseases; Viroids; Virus Replication; Viruses; Weight Loss; United States; China
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-020-2312-y

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 concern 1 . 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. Infection with SARS-CoV-2 causes interstitial pneumonia and viral replication in the lungs of transgenic mice that express a human version of ACE2, confirming the pathogenicity of the virus in this model.