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The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice.
Nature. 2020 07; 583(7818):830-833.Nat

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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Authors+Show Affiliations

Bao L
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Deng W
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Huang B
MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Gao H
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Liu J
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Ren L
Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China.
Wei Q
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Yu P
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Xu Y
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Qi F
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Qu Y
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Li F
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Lv Q
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Wang W
MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Xue J
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Gong S
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Liu M
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Wang G
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Wang S
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Song Z
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Zhao L
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Liu P
MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Zhao L
MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Ye F
MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Wang H
MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Zhou W
MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Zhu N
MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Zhen W
MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Yu H
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Zhang X
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Guo L
Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China.
Chen L
Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China.
Wang C
Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China.
Wang Y
Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China.
Wang X
Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China.
Xiao Y
Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China.
Sun Q
Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China.
Liu H
Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China.
Zhu F
Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China.
Ma C
Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China.
Yan L
Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China.
Yang M
Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China.
Han J
MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Xu W
MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Tan W
MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Peng X
Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China.
Jin Q
Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China.
Wu G
MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China. wugz@ivdc.chinacdc.cn.
Qin C
Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. qinchuan@pumc.edu.cn. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China. qinchuan@pumc.edu.cn.

MeSH

Angiotensin-Converting Enzyme 2AnimalsAntigens, ViralBetacoronavirusBronchiCOVID-19Coronavirus InfectionsDisease Models, AnimalEpithelial CellsFemaleHumansImmunoglobulin GLungLymphocytesMacrophages, AlveolarMaleMiceMice, TransgenicPandemicsPeptidyl-Dipeptidase APneumonia, ViralReceptors, Complement 3dSARS-CoV-2TransgenesVirus ReplicationWeight Loss

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32380511

Citation

Bao, Linlin, et al. "The Pathogenicity of SARS-CoV-2 in hACE2 Transgenic Mice." Nature, vol. 583, no. 7818, 2020, pp. 830-833.
Bao L, Deng W, Huang B, et al. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature. 2020;583(7818):830-833.
Bao, L., Deng, W., Huang, B., Gao, H., Liu, J., Ren, L., Wei, Q., Yu, P., Xu, Y., Qi, F., Qu, Y., Li, F., Lv, Q., Wang, W., Xue, J., Gong, S., Liu, M., Wang, G., Wang, S., ... Qin, C. (2020). The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature, 583(7818), 830-833. https://doi.org/10.1038/s41586-020-2312-y
Bao L, et al. The Pathogenicity of SARS-CoV-2 in hACE2 Transgenic Mice. Nature. 2020;583(7818):830-833. PubMed PMID: 32380511.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. AU - Bao,Linlin, AU - Deng,Wei, AU - Huang,Baoying, AU - Gao,Hong, AU - Liu,Jiangning, AU - Ren,Lili, AU - Wei,Qiang, AU - Yu,Pin, AU - Xu,Yanfeng, AU - Qi,Feifei, AU - Qu,Yajin, AU - Li,Fengdi, AU - Lv,Qi, AU - Wang,Wenling, AU - Xue,Jing, AU - Gong,Shuran, AU - Liu,Mingya, AU - Wang,Guanpeng, AU - Wang,Shunyi, AU - Song,Zhiqi, AU - Zhao,Linna, AU - Liu,Peipei, AU - Zhao,Li, AU - Ye,Fei, AU - Wang,Huijuan, AU - Zhou,Weimin, AU - Zhu,Na, AU - Zhen,Wei, AU - Yu,Haisheng, AU - Zhang,Xiaojuan, AU - Guo,Li, AU - Chen,Lan, AU - Wang,Conghui, AU - Wang,Ying, AU - Wang,Xinming, AU - Xiao,Yan, AU - Sun,Qiangming, AU - Liu,Hongqi, AU - Zhu,Fanli, AU - Ma,Chunxia, AU - Yan,Lingmei, AU - Yang,Mengli, AU - Han,Jun, AU - Xu,Wenbo, AU - Tan,Wenjie, AU - Peng,Xiaozhong, AU - Jin,Qi, AU - Wu,Guizhen, AU - Qin,Chuan, Y1 - 2020/05/07/ PY - 2020/02/02/received PY - 2020/04/24/accepted PY - 2020/5/8/pubmed PY - 2020/8/6/medline PY - 2020/5/8/entrez SP - 830 EP - 833 JF - Nature JO - Nature VL - 583 IS - 7818 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/32380511/The_pathogenicity_of_SARS_CoV_2_in_hACE2_transgenic_mice_ DB - PRIME DP - Unbound Medicine ER -