期刊
PLOS BIOLOGY
卷 19, 期 11, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.3001284
关键词
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资金
- NIAID of the NIH [AI153602, 1R21AI145400, R24AI120942, P51OD011132, R56 AI147623, U19AI090023]
- Clinical and Translational Science Award NRSA (TL1) Training Core from NIH [TL1TR001440]
- Institute of Human Infection and Immunity at UTMB COVID-19 Research Fund
- STARs Award by the University of Texas System
- McLaughlin Fellowship Fund at UTMB
- CDC
- Sealy & Smith Foundation
- Kleberg Foundation
- John S. Dunn Foundation
- Amon G. Carter Foundation
- Gilson Longenbaugh Foundation
- Summerfield Robert Foundation
- Emory Executive Vice President for Health Affairs Synergy Fund award
- Pediatric Research Alliance Center for Childhood Infections and Vaccines and Childrens Healthcare of Atlanta
- Woodruff Health Sciences Center
- Emory School of Medicine, Woodruff Health Sciences Center 2020 COVID-19 CURE Award
The study successfully generated a mouse-adapted strain of SARS-CoV-2 using a reverse genetic system, which recapitulates critical elements of human infection, including viral replication in the lung, immune cell infiltration, and significant in vivo disease.
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.
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