Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2

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  • Jiang, Ren-Di
    • Other Affiliation: Wuhan Institute of Virology
  • Liu, Mei-Qin
    • Other Affiliation: Wuhan Institute of Virology
  • Chen, Ying
    • Other Affiliation: Wuhan Institute of Virology
  • Shan, Chao
    • Other Affiliation: Wuhan Institute of Virology
  • Zhou, Yi-Wu
    • Other Affiliation: Wuhan Institute of Virology
  • Shen, Xu-Rui
    • Other Affiliation: Wuhan Institute of Virology
  • Li, Qian
    • Other Affiliation: Wuhan Institute of Virology
  • Zhang, Lei
    • Other Affiliation: Wuhan Institute of Virology
  • Zhu, Yan
    • Other Affiliation: Wuhan Institute of Virology
  • Si, Hao-Rui
    • Other Affiliation: Wuhan Institute of Virology
  • Wang, Qi
    • Other Affiliation: Wuhan Institute of Virology
  • Min, Juan
    • Other Affiliation: Wuhan Institute of Virology
  • Wang, Xi
    • Other Affiliation: Wuhan Institute of Virology
  • Zhang, Wei
    • Other Affiliation: Wuhan Institute of Virology
  • Li, Bei
    • Other Affiliation: Wuhan Institute of Virology
  • Zhang, Huan-Jun
    • Other Affiliation: Wuhan Institute of Virology
  • Baric, Ralph S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Zhou, Peng
    • Other Affiliation: Wuhan Institute of Virology
  • Yang, Xing-Lou
    • Other Affiliation: Wuhan Institute of Virology
  • Shi, Zheng-Li
    • Other Affiliation: Wuhan Institute of Virology
Abstract
  • COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human angiotensinconverting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Last, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics.
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  • Article
Rights statement
  • In Copyright
Journal title
  • Cell
Journal volume
  • 182
Page start
  • 50
Page end
  • 58
Language
  • English

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