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The Pathogenicity of SARS-CoV-2 in hACE2 Transgenic Mice

Linlin Bao, Wei Deng, Baoying Huang, Hong Gao, Jiangning Liu, Lili Ren, Qiang Wei, Pin Yu, Yanfeng Xu, Feifei Qi, Yajin Qu, Fengdi Li, Qi Lv, Wenling Wang, Jing Xue, Shuran Gong, Mingya Liu, Guanpeng Wang, Shunyi Wang, Zhiqi Song, Linna Zhao, Peipei Liu, Li Zhao, Fei Ye, Huijuan Wang, Weimin Zhou, Na Zhu, Wei Zhen, Haisheng Yu, Xiaojuan Zhang, Li Guo, Lan Chen, Conghui Wang, Ying Wang, Xinming Wang, Yan Xiao, Qiangming Sun, Hongqi Liu, Fanli Zhu, Chunxia Ma, Lingmei Yan, Mengli Yang, Jun Han, Wenbo Xu, Wenjie Tan, Xiaozhong Peng, Qi Jin, Guizhen Wu, Chuan Qin
doi: https://doi.org/10.1101/2020.02.07.939389
Linlin Bao
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Wei Deng
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Baoying Huang
2MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
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Hong Gao
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Jiangning Liu
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Lili Ren
3Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China
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Qiang Wei
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Pin Yu
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Yanfeng Xu
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Feifei Qi
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Yajin Qu
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Fengdi Li
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Qi Lv
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Wenling Wang
2MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
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Jing Xue
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Shuran Gong
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Mingya Liu
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Guanpeng Wang
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Shunyi Wang
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Zhiqi Song
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Linna Zhao
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Peipei Liu
2MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
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Li Zhao
2MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
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Fei Ye
2MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
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Huijuan Wang
2MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
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Weimin Zhou
2MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
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Na Zhu
2MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
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Wei Zhen
2MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
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Haisheng Yu
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Xiaojuan Zhang
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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Li Guo
3Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China
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Lan Chen
3Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China
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Conghui Wang
3Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China
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Ying Wang
3Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China
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Xinming Wang
3Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China
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Yan Xiao
3Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China
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Qiangming Sun
4Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China
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Hongqi Liu
4Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China
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Fanli Zhu
4Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China
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Chunxia Ma
4Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China
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Lingmei Yan
4Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China
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Mengli Yang
4Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China
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Jun Han
2MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
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Wenbo Xu
2MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
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Wenjie Tan
2MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
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Xiaozhong Peng
4Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China
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Qi Jin
3Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China
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Guizhen Wu
2MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
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  • For correspondence: qinchuan@pumc.edu.cn wugz@ivdc.chinacdc.cn
Chuan Qin
1Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
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  • For correspondence: qinchuan@pumc.edu.cn wugz@ivdc.chinacdc.cn
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Abstract

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the Corona Virus Disease 2019 (COVID-19) cases in China has become a public health emergency of international concern (PHEIC). Based on angiotensin converting enzyme 2 (ACE2) as cell entry receptor of SARS-CoV, we used the hACE2 transgenic mice infected with SARS-CoV-2 to study the pathogenicity of the virus. Weight loss and virus replication in lung were observed in hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of significant lymphocytes and monocytes in alveolar interstitium, and accumulation of macrophages in alveolar cavities. Viral antigens were observed in the bronchial epithelial cells, alveolar macrophages and alveolar epithelia. The phenomenon was not found in wild type mice with SARS-CoV-2 infection. The pathogenicity of SARS-CoV-2 in hACE2 mice was clarified and the Koch’s postulates were fulfilled as well, and the mouse model may facilitate the development of therapeutics and vaccines against SARS-CoV-2.

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Posted February 28, 2020.
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The Pathogenicity of SARS-CoV-2 in hACE2 Transgenic Mice
Linlin Bao, Wei Deng, Baoying Huang, Hong Gao, Jiangning Liu, Lili Ren, Qiang Wei, Pin Yu, Yanfeng Xu, Feifei Qi, Yajin Qu, Fengdi Li, Qi Lv, Wenling Wang, Jing Xue, Shuran Gong, Mingya Liu, Guanpeng Wang, Shunyi Wang, Zhiqi Song, Linna Zhao, Peipei Liu, Li Zhao, Fei Ye, Huijuan Wang, Weimin Zhou, Na Zhu, Wei Zhen, Haisheng Yu, Xiaojuan Zhang, Li Guo, Lan Chen, Conghui Wang, Ying Wang, Xinming Wang, Yan Xiao, Qiangming Sun, Hongqi Liu, Fanli Zhu, Chunxia Ma, Lingmei Yan, Mengli Yang, Jun Han, Wenbo Xu, Wenjie Tan, Xiaozhong Peng, Qi Jin, Guizhen Wu, Chuan Qin
bioRxiv 2020.02.07.939389; doi: https://doi.org/10.1101/2020.02.07.939389
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The Pathogenicity of SARS-CoV-2 in hACE2 Transgenic Mice
Linlin Bao, Wei Deng, Baoying Huang, Hong Gao, Jiangning Liu, Lili Ren, Qiang Wei, Pin Yu, Yanfeng Xu, Feifei Qi, Yajin Qu, Fengdi Li, Qi Lv, Wenling Wang, Jing Xue, Shuran Gong, Mingya Liu, Guanpeng Wang, Shunyi Wang, Zhiqi Song, Linna Zhao, Peipei Liu, Li Zhao, Fei Ye, Huijuan Wang, Weimin Zhou, Na Zhu, Wei Zhen, Haisheng Yu, Xiaojuan Zhang, Li Guo, Lan Chen, Conghui Wang, Ying Wang, Xinming Wang, Yan Xiao, Qiangming Sun, Hongqi Liu, Fanli Zhu, Chunxia Ma, Lingmei Yan, Mengli Yang, Jun Han, Wenbo Xu, Wenjie Tan, Xiaozhong Peng, Qi Jin, Guizhen Wu, Chuan Qin
bioRxiv 2020.02.07.939389; doi: https://doi.org/10.1101/2020.02.07.939389

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