OmniVira

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

Linlin Bao1,2 Wei Deng1,2 Baoying Huang3 Hong Gao1,2 Jiangning Liu1,2 Lili Ren4 Qiang Wei1,2 Pin Yu1,2 Yanfeng Xu1,2 Feifei Qi1,2 Yajin Qu1,2 Fengdi Li1,2 Qi Lv1,2 Wenling Wang3 Jing Xue1,2 Shuran Gong1,2 Mingya Liu1,2 Guanpeng Wang1,2 Shunyi Wang1,2 Zhiqi Song1,2 Linna Zhao1,2 Peipei Liu3 Li Zhao3 Fei Ye3 Huijuan Wang3 Weimin Zhou3 Na Zhu3 Wei Zhen3 Haisheng Yu1,2 Xiaojuan Zhang1,2 Li Guo4 Lan Chen4 Conghui Wang4 Ying Wang4 Xinming Wang4 Yan Xiao4 Qiangming Sun5 Hongqi Liu5 Fanli Zhu5 Chunxia Ma5 Lingmei Yan5 Mengli Yang5 Jun Han3 Wenbo Xu3 Wenjie Tan3 Xiaozhong Peng5 Qi Jin4 Guizhen Wu6 Chuan Qin7,8
Affiliations 8 institutions
  1. Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China.
  2. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China.
  3. MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
  4. Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China.
  5. Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China.
  6. MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China. [email protected].
  7. Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China. [email protected].
  8. NHC Key Laboratory of Human Disease Comparative Medicine, Comparative Medicine Center, Peking Union Medical College, Beijing, China. [email protected].
PMID32380511 DOI10.1038/s41586-020-2312-y Year2020 Journal Nature Languageeng Statusppublish

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.

Supporting text Virus Host Location
Transgenes 1 Angiotensin-Converting Enzyme 2 177 Animals 1948 Antigens, Viral 49 Betacoronavirus 78 Bronchi 6 Coronavirus Infections 171 COVID-19 425 Disease Models, Animal 77 Epithelial Cells 27 Female 289 Humans 1440 Immunoglobulin G 24 Lung 65 Lymphocytes 1 Macrophages, Alveolar 2 Male 224 Mice 253 Mice, Transgenic 13 Pandemics 108 Peptidyl-Dipeptidase A 57 Pneumonia, Viral 42 Receptors, Complement 3d 1 SARS-CoV-2 453

Evidence records

1 total
Experimental Infection
1 records · 1 evidence types
Evidence type Pathogenicity Experiment
1 records
OVE11566 Pathogenicity Experiment
Key finding

Experimental infection of hACE2 transgenic mice with SARS-CoV-2 caused weight loss, lung viral replication, and interstitial pneumonia with immune cell infiltration, confirming viral pathogenicity in this model.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
house mouse Mus musculus Experimental system
Location
Not specified
Supporting text

We infected transgenic mice that express human ACE2 (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.

Method
experimental infection | histopathology | virus detection in lungs
Experimental system
hACE2 transgenic mouse infection model