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

Cell. 2020 Jul 9;182(1):50-58.e8. doi: 10.1016/j.cell.2020.05.027. Epub 2020 May 21.


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 angiotensin-converting 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.

Keywords: COVID-19; SARS-CoV-2; human ACE2 transgenic mouse; pneumonia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Betacoronavirus / physiology*
  • COVID-19
  • Coronavirus Infections / pathology*
  • Disease Models, Animal*
  • Female
  • Humans
  • Lung Diseases, Interstitial / pathology
  • Lung Diseases, Interstitial / virology
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic* / genetics
  • Pandemics
  • Peptidyl-Dipeptidase A / genetics
  • Pneumonia, Viral / pathology*
  • SARS-CoV-2
  • Viral Tropism
  • Weight Loss


  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2