학술논문
Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge.
Document Type
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
Source
PLoS Biology, Vol 19, Iss 11, p e3001284 (2021)
Subject
Language
English
ISSN
1544-9173
1545-7885
1545-7885
Abstract
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.