Open AccessPathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2
Author(s) -
Ren-Di Jiang,
Mei-Qin Liu,
Ying Chen,
Chao Shan,
Yi-Wu Zhou,
Xu-Rui Shen,
Qian Li,
Lei Zhang,
Yan Zhu,
Hao-Rui Si,
Qi Wang,
Juan Min,
Xi Wang,
Wei Zhang,
Bei Li,
Huajun Zhang,
Ralph S. Baric,
Peng Zhou,
XingLou Yang,
ZhengLi Shi
Publication year - 2020
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2020.05.027
Subject(s) - biology , pathogenesis , virology , angiotensin converting enzyme 2 , transgene , covid-19 , genetically modified mouse , enzyme , gene , genetics , immunology , disease , medicine , biochemistry , infectious disease (medical specialty) , outbreak
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.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom