Open AccessMouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge
Author(s) -
Antonio E. Muruato,
Michelle N Vu,
Bryan A. Johnson,
Meredith E. Davis-Gardner,
Abigail Vanderheiden,
Kumari G. Lokugamage,
Craig Schindewolf,
Patricia A. CrocquetValdes,
Rose M. Langsjoen,
Jessica A. Plante,
Kenneth S. Plante,
Scott C. Weaver,
Kari Debbink,
Andrew Routh,
David H. Walker,
Mehul S. Suthar,
Pei–Yong Shi,
Xuping Xie,
Vineet D. Menachery
Publication year - 2021
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3001284
Subject(s) - biology , coronavirus , virology , viral replication , immune system , pandemic , heterologous , immunity , virus , immunology , disease , infectious disease (medical specialty) , covid-19 , genetics , gene , medicine , pathology
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.