A novel hACE2 knock-in mouse model recapitulates pulmonary and intestinal SARS-CoV-2 infection

Frontiers in Microbiology

Microbiology

Weiyang Sun¹  Yuwei Gao¹  Xiaoyan Ding²  Jintao Li²  Yunkai Zhu²  Ruixuan Wang²  Minyue Qiu²  Xiaoyang Zhou²  Peng Xie²  Yu Zhang²  Hui Wang³  Hongjing Gu³ 

[1] Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China;Department of Biosafety, School of Basic Medicine, Army Medical University, Chongqing, China;State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, China;

关键词: mouse model;    intestinal infection;    SARS-CoV-2;    immune cells;    pneumonia;   

DOI  :  10.3389/fmicb.2023.1175188

 received in 2023-02-27, accepted in 2023-05-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is responsible for the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter the host, and the gastrointestinal tract is a potential infection site as this receptor is expressed on it. Multiple studies have indicated that an increasing number of COVID-19 patients presented with gastrointestinal symptoms that are highly associated with disease severity. Moreover, emerging evidence has demonstrated that alterations in the gut immune microenvironment induced by intestinal SARS-CoV-2 infection can regulate respiratory symptoms. Therefore, targeting the intestines may be a candidate therapeutic strategy in patients with COVID-19; however, no mouse model can serve as an appropriate infection model for the development of fatal pneumonia while mimicking intestinal infection. In this study, a novel human ACE2 knock-in (KI) mouse model (or hACE2-KI) was systemically compared with the popular K18-hACE2 mice; it showed differences in the distribution of lung and intestinal infections and pathophysiological characteristics. These newly generated hACE2-KI mice were susceptible to intranasal infection with SARS-CoV-2, and not only developed mild to severe lung injury, but also acquired intestinal infection. Consequently, this model can be a useful tool for studying intestinal SARS-CoV-2 infection and developing effective therapeutic strategies.

【 授权许可】

Unknown   
Copyright © 2023 Zhou, Sun, Zhang, Gu, Wang, Xie, Zhu, Qiu, Ding, Wang, Gao and Li.