Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge.

The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a pandemic causing significant damage to public health and the economy. Efforts to understand the mechanisms of Coronavirus Disease 2019 (COVID-19) have been hampered by the lack of robust mouse models. To...

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Autores principales: Antonio Muruato, Michelle N Vu, Bryan A Johnson, Meredith E Davis-Gardner, Abigail Vanderheiden, Kumari Lokugamage, Craig Schindewolf, Patricia A Crocquet-Valdes, Rose M Langsjoen, Jessica A Plante, Kenneth S Plante, Scott C Weaver, Kari Debbink, Andrew L Routh, David Walker, Mehul S Suthar, Pei-Yong Shi, Xuping Xie, Vineet D Menachery
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Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/f88b62f8b785486da6cd64a014ea3fc2
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spelling oai:doaj.org-article:f88b62f8b785486da6cd64a014ea3fc22021-12-02T19:54:34ZMouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge.1544-91731545-788510.1371/journal.pbio.3001284https://doaj.org/article/f88b62f8b785486da6cd64a014ea3fc22021-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001284https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a pandemic causing significant damage to public health and the economy. Efforts to understand the mechanisms of Coronavirus Disease 2019 (COVID-19) have been hampered by the lack of robust mouse models. To overcome this barrier, we used a reverse genetic system to generate a mouse-adapted strain of SARS-CoV-2. Incorporating key mutations found in SARS-CoV-2 variants, this model recapitulates critical elements of human infection including viral replication in the lung, immune cell infiltration, and significant in vivo disease. Importantly, mouse adaptation of SARS-CoV-2 does not impair replication in human airway cells and maintains antigenicity similar to human SARS-CoV-2 strains. Coupled with the incorporation of mutations found in variants of concern, CMA3p20 offers several advantages over other mouse-adapted SARS-CoV-2 strains. Using this model, we demonstrate that SARS-CoV-2-infected mice are protected from lethal challenge with the original Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), suggesting immunity from heterologous Coronavirus (CoV) strains. Together, the results highlight the use of this mouse model for further study of SARS-CoV-2 infection and disease.Antonio MuruatoMichelle N VuBryan A JohnsonMeredith E Davis-GardnerAbigail VanderheidenKumari LokugamageCraig SchindewolfPatricia A Crocquet-ValdesRose M LangsjoenJessica A PlanteKenneth S PlanteScott C WeaverKari DebbinkAndrew L RouthDavid WalkerMehul S SutharPei-Yong ShiXuping XieVineet D MenacheryPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 11, p e3001284 (2021)
institution DOAJ
collection DOAJ
language EN
topic Biology (General)
QH301-705.5
spellingShingle Biology (General)
QH301-705.5
Antonio Muruato
Michelle N Vu
Bryan A Johnson
Meredith E Davis-Gardner
Abigail Vanderheiden
Kumari Lokugamage
Craig Schindewolf
Patricia A Crocquet-Valdes
Rose M Langsjoen
Jessica A Plante
Kenneth S Plante
Scott C Weaver
Kari Debbink
Andrew L Routh
David Walker
Mehul S Suthar
Pei-Yong Shi
Xuping Xie
Vineet D Menachery
Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge.
description The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a pandemic causing significant damage to public health and the economy. Efforts to understand the mechanisms of Coronavirus Disease 2019 (COVID-19) have been hampered by the lack of robust mouse models. To overcome this barrier, we used a reverse genetic system to generate a mouse-adapted strain of SARS-CoV-2. Incorporating key mutations found in SARS-CoV-2 variants, this model recapitulates critical elements of human infection including viral replication in the lung, immune cell infiltration, and significant in vivo disease. Importantly, mouse adaptation of SARS-CoV-2 does not impair replication in human airway cells and maintains antigenicity similar to human SARS-CoV-2 strains. Coupled with the incorporation of mutations found in variants of concern, CMA3p20 offers several advantages over other mouse-adapted SARS-CoV-2 strains. Using this model, we demonstrate that SARS-CoV-2-infected mice are protected from lethal challenge with the original Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), suggesting immunity from heterologous Coronavirus (CoV) strains. Together, the results highlight the use of this mouse model for further study of SARS-CoV-2 infection and disease.
format article
author Antonio Muruato
Michelle N Vu
Bryan A Johnson
Meredith E Davis-Gardner
Abigail Vanderheiden
Kumari Lokugamage
Craig Schindewolf
Patricia A Crocquet-Valdes
Rose M Langsjoen
Jessica A Plante
Kenneth S Plante
Scott C Weaver
Kari Debbink
Andrew L Routh
David Walker
Mehul S Suthar
Pei-Yong Shi
Xuping Xie
Vineet D Menachery
author_facet Antonio Muruato
Michelle N Vu
Bryan A Johnson
Meredith E Davis-Gardner
Abigail Vanderheiden
Kumari Lokugamage
Craig Schindewolf
Patricia A Crocquet-Valdes
Rose M Langsjoen
Jessica A Plante
Kenneth S Plante
Scott C Weaver
Kari Debbink
Andrew L Routh
David Walker
Mehul S Suthar
Pei-Yong Shi
Xuping Xie
Vineet D Menachery
author_sort Antonio Muruato
title Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge.
title_short Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge.
title_full Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge.
title_fullStr Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge.
title_full_unstemmed Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge.
title_sort mouse-adapted sars-cov-2 protects animals from lethal sars-cov challenge.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/f88b62f8b785486da6cd64a014ea3fc2
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