Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.

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 afte...

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Main Authors: Cheng-Pu 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, Yen-Hui Chen, Yi-An Ko, Chun-Che Liao, Liang-Yu Chen, I-Jung Lee, Szu-I Tsung, Yun-Ju Lai, Ming-Tsai Chiang, Jian-Jong Liang, Wen-Chun Liu, Jing-Rong Wang, Joyce Pei-Yi Yuan, Yin-Shiou Lin, Yi-Ching Tsai, Shie-Liang Hsieh, Chia-Wei Li, Han-Chung Wu, Tai-Ming Ko, Yi-Ling Lin, Mi-Hua Tao
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-08-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1009758
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author Cheng-Pu 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
Yen-Hui Chen
Yi-An Ko
Chun-Che Liao
Liang-Yu Chen
I-Jung Lee
Szu-I Tsung
Yun-Ju Lai
Ming-Tsai Chiang
Jian-Jong Liang
Wen-Chun Liu
Jing-Rong Wang
Joyce Pei-Yi Yuan
Yin-Shiou Lin
Yi-Ching Tsai
Shie-Liang Hsieh
Chia-Wei Li
Han-Chung Wu
Tai-Ming Ko
Yi-Ling Lin
Mi-Hua Tao
author_facet Cheng-Pu 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
Yen-Hui Chen
Yi-An Ko
Chun-Che Liao
Liang-Yu Chen
I-Jung Lee
Szu-I Tsung
Yun-Ju Lai
Ming-Tsai Chiang
Jian-Jong Liang
Wen-Chun Liu
Jing-Rong Wang
Joyce Pei-Yi Yuan
Yin-Shiou Lin
Yi-Ching Tsai
Shie-Liang Hsieh
Chia-Wei Li
Han-Chung Wu
Tai-Ming Ko
Yi-Ling Lin
Mi-Hua Tao
author_sort Cheng-Pu Sun
collection DOAJ
description 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.
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spelling doaj.art-4c7d04f4f9e34a85ac0d0588129271b22022-12-21T19:18:15ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-08-01178e100975810.1371/journal.ppat.1009758Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.Cheng-Pu SunJia-Tsrong JanI-Hsuan WangHsiu-Hua MaHui-Ying KoPing-Yi WuTzu-Jiun KuoHsin-Ni LiaoYu-Hua LanZong-Lin SieYen-Hui ChenYi-An KoChun-Che LiaoLiang-Yu ChenI-Jung LeeSzu-I TsungYun-Ju LaiMing-Tsai ChiangJian-Jong LiangWen-Chun LiuJing-Rong WangJoyce Pei-Yi YuanYin-Shiou LinYi-Ching TsaiShie-Liang HsiehChia-Wei LiHan-Chung WuTai-Ming KoYi-Ling LinMi-Hua TaoSince 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.https://doi.org/10.1371/journal.ppat.1009758
spellingShingle Cheng-Pu 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
Yen-Hui Chen
Yi-An Ko
Chun-Che Liao
Liang-Yu Chen
I-Jung Lee
Szu-I Tsung
Yun-Ju Lai
Ming-Tsai Chiang
Jian-Jong Liang
Wen-Chun Liu
Jing-Rong Wang
Joyce Pei-Yi Yuan
Yin-Shiou Lin
Yi-Ching Tsai
Shie-Liang Hsieh
Chia-Wei Li
Han-Chung Wu
Tai-Ming Ko
Yi-Ling Lin
Mi-Hua Tao
Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.
PLoS Pathogens
title Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.
title_full Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.
title_fullStr Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.
title_full_unstemmed Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.
title_short Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.
title_sort rapid generation of mouse model for emerging infectious disease with the case of severe covid 19
url https://doi.org/10.1371/journal.ppat.1009758
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