An inducible hACE2 transgenic mouse model recapitulates SARS-CoV-2 infection and pathogenesis in vivo.
Kuo LiuMuxue TangWei XuXinfeng MengHengwei JinMaoying HanJing PuYutang LiFanke JiaoRuilin SunRuling ShenKathy O LuiLu LuBin ZhouPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
The classical manifestation of COVID-19 is pulmonary infection. After host cell entry via human angiotensin-converting enzyme II (hACE2), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can infect pulmonary epithelial cells, especially the AT2 (alveolar type II) cells that are crucial for maintaining normal lung function. However, previous hACE2 transgenic models have failed to specifically and efficiently target the cell types that express hACE2 in humans, especially AT2 cells. In this study, we report an inducible, transgenic hACE2 mouse line and showcase three examples for specifically expressing hACE2 in three different lung epithelial cells, including AT2 cells, club cells, and ciliated cells. Moreover, all these mice models develop severe pneumonia after SARS-CoV-2 infection. This study demonstrates that the hACE2 model can be used to precisely study any cell type of interest with regard to COVID-19-related pathologies.
Keyphrases
- sars cov
- induced apoptosis
- respiratory syndrome coronavirus
- cell cycle arrest
- coronavirus disease
- lung function
- mouse model
- single cell
- cell death
- angiotensin converting enzyme
- endothelial cells
- cell proliferation
- oxidative stress
- cystic fibrosis
- adipose tissue
- type diabetes
- air pollution
- skeletal muscle
- extracorporeal membrane oxygenation