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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Public Library of Science (PLoS)
2021
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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) |
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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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