Open AccessRapid generation of mouse model for emerging infectious disease with the case of severe COVID-19
Author(s) -
ChengPu Sun,
Jia-Tsrong Jan,
I-Hsuan Wang,
Hsiu-Hua Ma,
Hui-Ying Ko,
Ping-Yi Wu,
Tzu-Jiun Kuo,
Hsin-Ni Liao,
Yu-Hua Lan,
Zong-Lin Sie,
YenHui Chen,
Yi-An Ko,
Chun-Che Liao,
Liang-Yu Chen,
I-Jung Lee,
Szu-I Tsung,
YunJu Lai,
MingTsai Chiang,
Jian-Jong Liang,
Wen-Chun Liu,
JingRong Wang,
Joyce Pei-Yi Yuan,
Yin-Shiou Lin,
Yi-Ching Tsai,
Shie Liang Hsieh,
Chia-Wei Li,
HanChung Wu,
TaiMing Ko,
Yi-Ling Lin,
MiHua Tao
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009758
Subject(s) - covid-19 , virology , virus , infectious disease (medical specialty) , pathophysiology , disease , biology , immunology , pandemic , recombinant dna , receptor , medicine , gene , endocrinology , biochemistry
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.