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

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

doi:10.1371/journal.ppat.1009758

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

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 LiuJing 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

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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.

Original language	English
Article number	e1009758
Journal	PLoS Pathogens
Volume	17
Issue number	8
DOIs	https://doi.org/10.1371/journal.ppat.1009758
State	Published - Aug 2021
Externally published	Yes

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Sun, C. P., Jan, J. T., Wang, I. H., Ma, H. H., Ko, H. Y., Wu, P. Y., Kuo, T. J., Liao, H. N., Lan, Y. H., Sie, Z. L., Chen, Y. H., Ko, Y. A., Liao, C. C., Chen, L. Y., Lee, I. J., Tsung, S. I., Lai, Y. J., Chiang, M. T., Liang, J. J., ... Tao, M. H. (2021). Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19. PLoS Pathogens, 17(8), Article e1009758. https://doi.org/10.1371/journal.ppat.1009758

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title = "Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19",

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 = "Sun, {Cheng Pu} and Jan, {Jia Tsrong} and Wang, {I. Hsuan} and Ma, {Hsiu Hua} and Ko, {Hui Ying} and Wu, {Ping Yi} and Kuo, {Tzu Jiun} and Liao, {Hsin Ni} and Lan, {Yu Hua} and Sie, {Zong Lin} and Chen, {Yen Hui} and Ko, {Yi An} and Liao, {Chun Che} and Chen, {Liang Yu} and Lee, {I. Jung} and Tsung, {Szu I.} and Lai, {Yun Ju} and Chiang, {Ming Tsai} and Liang, {Jian Jong} and Liu, {Wen Chun} and Wang, {Jing Rong} and Yuan, {Joyce Pei Yi} and Lin, {Yin Shiou} and Tsai, {Yi Ching} and Hsieh, {Shie Liang} and Li, {Chia Wei} and Wu, {Han Chung} and Ko, {Tai Ming} and Lin, {Yi Ling} and Tao, {Mi Hua}",

note = "Publisher Copyright: {\textcopyright} 2021 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2021",

month = aug,

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Sun, CP, Jan, JT, Wang, IH, Ma, HH, Ko, HY, Wu, PY, Kuo, TJ, Liao, HN, Lan, YH, Sie, ZL, Chen, YH, Ko, YA, Liao, CC, Chen, LY, Lee, IJ, Tsung, SI, Lai, YJ, Chiang, MT, Liang, JJ, Liu, WC, Wang, JR, Yuan, JPY, Lin, YS, Tsai, YC, Hsieh, SL, Li, CW, Wu, HC, Ko, TM, Lin, YL & Tao, MH 2021, 'Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19', PLoS Pathogens, vol. 17, no. 8, e1009758. https://doi.org/10.1371/journal.ppat.1009758

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AU - Sun, Cheng Pu

AU - Jan, Jia Tsrong

AU - Wang, I. Hsuan

AU - Ma, Hsiu Hua

AU - Ko, Hui Ying

AU - Wu, Ping Yi

AU - Kuo, Tzu Jiun

AU - Liao, Hsin Ni

AU - Lan, Yu Hua

AU - Sie, Zong Lin

AU - Chen, Yen Hui

AU - Ko, Yi An

AU - Liao, Chun Che

AU - Chen, Liang Yu

AU - Lee, I. Jung

AU - Tsung, Szu I.

AU - Lai, Yun Ju

AU - Chiang, Ming Tsai

AU - Liang, Jian Jong

AU - Liu, Wen Chun

AU - Wang, Jing Rong

AU - Yuan, Joyce Pei Yi

AU - Lin, Yin Shiou

AU - Tsai, Yi Ching

AU - Hsieh, Shie Liang

AU - Li, Chia Wei

AU - Wu, Han Chung

AU - Ko, Tai Ming

AU - Lin, Yi Ling

AU - Tao, Mi Hua

N1 - Publisher Copyright: © 2021 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2021/8

Y1 - 2021/8

N2 - 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.

AB - 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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DO - 10.1371/journal.ppat.1009758

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VL - 17

JO - PLoS Pathogens

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ER -

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

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