We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.
- Authors
Sun, Cheng-Pu; Jan, Jia-Tsrong; Wang, I-Hsuan; Ma, Hsiu-Hua; Ko, Hui-Ying; Wu, Ping-Yi; Kuo, Tzu-Jiun; Liao, Hsin-Ni; Lan, Yu-Hua; Sie, Zong-Lin; Chen, Yen-Hui; Ko, Yi-An; Liao, Chun-Che; Chen, Liang-Yu; Lee, I-Jung; Tsung, Szu-I; Lai, Yun-Ju; Chiang, Ming-Tsai; Liang, Jian-Jong; Liu, Wen-Chun
- Abstract
Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development. Author summary: Upon the emergence of new infectious disease, animal model becomes a pivotal tool for study of disease mechanism and development of therapeutics. In this study, we propose a versatile approach that allows rapid generation of mouse model for novel infectious disease once the receptor of the pathogen is identified. We demonstrated this approach by generating a mouse model for COVID-19 in a month's time. These mice were capable of recapitulating severe COVID-19 in patients, and successfully applied in the development of a therapeutic antibody cocktail for the disease. This not only suggests the usefulness of this mouse model for the research on COVID-19, but also exhibit the utility of the proposed approach for establishing animal model for infectious disease.
- Subjects
LABORATORY mice; COVID-19 pandemic; EMERGING infectious diseases; COVID-19; ANIMAL disease models; SARS-CoV-2
- Publication
PLoS Pathogens, 2021, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1009758