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...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2021-08-01
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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. |
first_indexed | 2024-12-21T02:58:39Z |
format | Article |
id | doaj.art-4c7d04f4f9e34a85ac0d0588129271b2 |
institution | Directory Open Access Journal |
issn | 1553-7366 1553-7374 |
language | English |
last_indexed | 2024-12-21T02:58:39Z |
publishDate | 2021-08-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS Pathogens |
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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