The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice
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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 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.
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Investigators found viral replication in a number of organs with the highest expression in the lung and brain and increased serum cytokines including IFNγ; however, the mouse background used in these models was C57BL/6, which responds to antigens with elevated Th1-type immune responses because they have few mast cells.
“Investigators found viral replication in a number of organs with the highest expression in the lung and brain and increased serum cytokines including IFN γ ; however, the mouse background used in these models was C57BL/6, which responds to antigens with elevated Th1-type immune responses because they have few mast cells. 160,177,178”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [177]
Split into 2 atoms — 0 confirmed, 0 partially supported, 2 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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Experimental — accuracy not yet measuredThe ACE2 receptor is significantly different between mice and humans; so mouse models most often use a humanized ACE2 or lung passage to overcome this obstacle.
“Although mouse models have the most information available about their biology and many research tools, the ACE2 receptor is significantly different between mice and humans; so mouse models most often use a humanized ACE2 or lung passage to overcome this obstacle. 177-179”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [177]
The Mouse experiments section describes mice engineered to express human ACE2, and the main text reports viral replication in those mice but not in infected wild-type mice. The paper does not establish that mouse and human ACE2 are significantly different, that mouse models most often use humanized ACE2, or that lung passage is an alternative used to overcome this obstacle. No page number is provided for these passages. (LLM, conf=0.87)
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Self-citation
- Authors
- 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., Song, Z., Zhao, L., Liu, P., Zhao, L., Ye, F., Wang, H., Zhou, W., Zhu, N., Zhen, W., Yu, H., Zhang, X., Guo, L., Chen, L., Wang, C., Wang, Y., Wang, X., Xiao, Y., Sun, Q., Liu, H., Zhu, F., Ma, C., Yan, L., Yang, M., Han, J., Xu, W., Tan, W., Peng, X., Jin, Q., Wu, G., & Qin, C.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Chinese Center For Disease Control and Prevention (CN)
- Corresponding author
- Wu, Guizhen
- Qin, Chuan
- ORCID
- Bao, Linlin
- Deng, Wei
- Huang, Baoying
- Gao, Hong
- Liu, Jiangning
- Ren, Lili
- Wei, Qiang
- Xu, Yanfeng
- Qu, Yajin
- Lv, Qi
- 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
- Yu, Haisheng
- Zhang, Xiaojuan
- Guo, Li
- Wang, Conghui
- Wang, Ying
- Xiao, Yan
- Sun, Qiangming
- Liu, Hongqi
- Yang, Mengli
- Han, Jun
- Xu, Wenbo
- Tan, Wenjie
- Peng, Xiaozhong
- Jin, Qi
- Wu, Guizhen
- Qin, Chuan
- Venue
- Nature
- Published
- 2020-05-07
- Volume
- 583
- Issue
- 7818
- Pages
- 830-833
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3021880084
- Cited by
- 1,126
- References
- 10
- Citations by year
- 2026: 33 · 2025: 59 · 2024: 86 · 2023: 117 · 2022: 222 · 2021: 325 · 2020: 284
- FWCI
- 31.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Peking Union Medical College
- Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2016-I2M-2–006)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, hACE2 transgenic mice, human ACE2, viral pathogenicity, interstitial lung disease, lung viral replication, bronchial epithelial cells, alveolar macrophages, viral antigen distribution, weight loss
- MeSH terms
- Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Animals, Antigens, Viral, Bronchi, Disease Models, Animal, Epithelial Cells, Female, Humans, Immunoglobulin G, Peptidyl-Dipeptidase A, Lung, Lymphocytes, Male, Mice, Transgenic, Pneumonia, Viral, Virus Replication, Weight Loss, Macrophages, Alveolar, Receptors, Complement 3d, Coronavirus Infections, Transgenes, Mice, Pandemics
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