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

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


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

AbstractSevere acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the corona virus disease 2019 (COVID-19) cases in China and has become a public health emergency of international concern1. Because angiotensin-converting enzyme 2 (ACE2) is the cell entry receptor of SARS-CoV5, we used transgenic mice bearing human ACE2 and infected with SARS-CoV-2 to study the pathogenicity of the…

Abstract

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the corona virus disease 2019 (COVID-19) cases in China and has become a public health emergency of international concern1. Because angiotensin-converting enzyme 2 (ACE2) is the cell entry receptor of SARS-CoV5, we used transgenic mice bearing human ACE2 and 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 macrophages and lymphocytes into the alveolar interstitium, and accumulation of macrophages in alveolar cavities. Viral antigens were observed in the bronchial epithelial cells, macrophages and alveolar epithelia. The phenomenon was not found in wild-type mice with SARS-CoV-2 infection. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. The mouse model with SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutics and vaccines as well as understanding the pathogenesis of COVID-19.

Change history


  • 14 May 2020

    Readers are alerted that there are some anomalies in figure presentation in this paper. We are investigating and appropriate editorial action will be taken once this matter is resolved.

Author information

Author notes

  1. These authors contributed equally: Linlin Bao, Wei Deng, Baoying Huang, Hong Gao, Jiangning Liu

Affiliations

  1. NHC Key Laboratory of Human Disease Comparative Medicine, 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
    • Linlin Bao
    • , Wei Deng
    • , Hong Gao
    • , Jiangning Liu
    • , Qiang Wei
    • , Pin Yu
    • , Yanfeng Xu
    • , Feifei Qi
    • , Yajin Qu
    • , Fengdi Li
    • , Qi Lv
    • , Jing Xue
    • , Shuran Gong
    • , Mingya Liu
    • , Guanpeng Wang
    • , Shunyi Wang
    • , Zhiqi Song
    • , Linna Zhao
    • , Haisheng Yu
    • , Xiaojuan Zhang
    •  & Chuan Qin
  2. MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
    • Baoying Huang
    • , Wenling Wang
    • , Peipei Liu
    • , Li Zhao
    • , Fei Ye
    • , Huijuan Wang
    • , Weimin Zhou
    • , Na Zhu
    • , Wei Zhen
    • , Jun Han
    • , Wenbo Xu
    • , Wenjie Tan
    •  & Guizhen Wu
  3. Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China
    • Lili Ren
    • , Li Guo
    • , Lan Chen
    • , Conghui Wang
    • , Ying Wang
    • , Xinming Wang
    • , Yan Xiao
    •  & Qi Jin
  4. Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China
    • Qiangming Sun
    • , Hongqi Liu
    • , Fanli Zhu
    • , Chunxia Ma
    • , Lingmei Yan
    • , Mengli Yang
    •  & Xiaozhong Peng

Authors

  1. Linlin Bao

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  2. Wei Deng

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  3. Baoying Huang

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  4. Hong Gao

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  5. Jiangning Liu

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  6. Lili Ren

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  7. Qiang Wei

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  8. Pin Yu

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  9. Yanfeng Xu

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  10. Feifei Qi

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  11. Yajin Qu

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  12. Fengdi Li

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  13. Qi Lv

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  14. Wenling Wang

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  15. Jing Xue

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  16. Shuran Gong

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  17. Mingya Liu

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  18. Guanpeng Wang

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  19. Shunyi Wang

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  20. Zhiqi Song

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  21. Linna Zhao

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  22. Peipei Liu

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  23. Li Zhao

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  24. Fei Ye

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  25. Huijuan Wang

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  26. Weimin Zhou

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  27. Na Zhu

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  28. Wei Zhen

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  29. Haisheng Yu

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  30. Xiaojuan Zhang

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  31. Li Guo

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  32. Lan Chen

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  33. Conghui Wang

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  34. Ying Wang

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  35. Xinming Wang

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  36. Yan Xiao

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  37. Qiangming Sun

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  38. Hongqi Liu

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  39. Fanli Zhu

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  40. Chunxia Ma

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  41. Lingmei Yan

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  42. Mengli Yang

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  43. Jun Han

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  44. Wenbo Xu

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  45. Wenjie Tan

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  46. Xiaozhong Peng

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  47. Qi Jin

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  48. Guizhen Wu

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  49. Chuan Qin

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Corresponding authors

Correspondence to
Guizhen Wu or Chuan Qin.

Supplementary information

About this article

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Cite this article

Bao, L., Deng, W., Huang, B. et al. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice.
Nature (2020). https://doi.org/10.1038/s41586-020-2312-y

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Uncategorized

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

AbstractSevere acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the corona virus disease 2019 (COVID-19) cases in China and has become a public health emergency of international concern1. Because angiotensin-converting enzyme 2 (ACE2) is the cell entry receptor of SARS-CoV5, we used transgenic mice bearing human ACE2 and infected with SARS-CoV-2 to study the pathogenicity of the…

Abstract

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the corona virus disease 2019 (COVID-19) cases in China and has become a public health emergency of international concern1. Because angiotensin-converting enzyme 2 (ACE2) is the cell entry receptor of SARS-CoV5, we used transgenic mice bearing human ACE2 and 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 macrophages and lymphocytes into the alveolar interstitium, and accumulation of macrophages in alveolar cavities. Viral antigens were observed in the bronchial epithelial cells, macrophages and alveolar epithelia. The phenomenon was not found in wild-type mice with SARS-CoV-2 infection. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. The mouse model with SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutics and vaccines as well as understanding the pathogenesis of COVID-19.

Change history


  • 14 May 2020

    Readers are alerted that there are some anomalies in figure presentation in this paper. We are investigating and appropriate editorial action will be taken once this matter is resolved.

Author information

Author notes

  1. These authors contributed equally: Linlin Bao, Wei Deng, Baoying Huang, Hong Gao, Jiangning Liu

Affiliations

  1. NHC Key Laboratory of Human Disease Comparative Medicine, 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
    • Linlin Bao
    • , Wei Deng
    • , Hong Gao
    • , Jiangning Liu
    • , Qiang Wei
    • , Pin Yu
    • , Yanfeng Xu
    • , Feifei Qi
    • , Yajin Qu
    • , Fengdi Li
    • , Qi Lv
    • , Jing Xue
    • , Shuran Gong
    • , Mingya Liu
    • , Guanpeng Wang
    • , Shunyi Wang
    • , Zhiqi Song
    • , Linna Zhao
    • , Haisheng Yu
    • , Xiaojuan Zhang
    •  & Chuan Qin
  2. MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
    • Baoying Huang
    • , Wenling Wang
    • , Peipei Liu
    • , Li Zhao
    • , Fei Ye
    • , Huijuan Wang
    • , Weimin Zhou
    • , Na Zhu
    • , Wei Zhen
    • , Jun Han
    • , Wenbo Xu
    • , Wenjie Tan
    •  & Guizhen Wu
  3. Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China
    • Lili Ren
    • , Li Guo
    • , Lan Chen
    • , Conghui Wang
    • , Ying Wang
    • , Xinming Wang
    • , Yan Xiao
    •  & Qi Jin
  4. Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing, China
    • Qiangming Sun
    • , Hongqi Liu
    • , Fanli Zhu
    • , Chunxia Ma
    • , Lingmei Yan
    • , Mengli Yang
    •  & Xiaozhong Peng

Authors

  1. Linlin Bao

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  2. Wei Deng

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  3. Baoying Huang

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  4. Hong Gao

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  5. Jiangning Liu

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  6. Lili Ren

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  7. Qiang Wei

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  8. Pin Yu

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  9. Yanfeng Xu

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  10. Feifei Qi

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  11. Yajin Qu

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  12. Fengdi Li

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  13. Qi Lv

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  14. Wenling Wang

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  15. Jing Xue

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  16. Shuran Gong

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  17. Mingya Liu

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  18. Guanpeng Wang

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  19. Shunyi Wang

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  20. Zhiqi Song

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  21. Linna Zhao

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  22. Peipei Liu

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  23. Li Zhao

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  24. Fei Ye

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  25. Huijuan Wang

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  26. Weimin Zhou

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  27. Na Zhu

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  28. Wei Zhen

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  29. Haisheng Yu

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  30. Xiaojuan Zhang

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  31. Li Guo

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  32. Lan Chen

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  33. Conghui Wang

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  34. Ying Wang

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  35. Xinming Wang

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  36. Yan Xiao

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  37. Qiangming Sun

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  38. Hongqi Liu

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  39. Fanli Zhu

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  40. Chunxia Ma

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  41. Lingmei Yan

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  42. Mengli Yang

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  43. Jun Han

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  44. Wenbo Xu

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  45. Wenjie Tan

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  46. Xiaozhong Peng

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  47. Qi Jin

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  48. Guizhen Wu

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  49. Chuan Qin

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Corresponding authors

Correspondence to
Guizhen Wu or Chuan Qin.

Supplementary information

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bao, L., Deng, W., Huang, B. et al. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice.
Nature (2020). https://doi.org/10.1038/s41586-020-2312-y

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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