Characterization of Collaborative Cross mouse founder strain CAST/EiJ as a novel model for lethal COVID-19
Mutations in SARS-CoV-2 variants of concern (VOCs) have expanded the viral host range beyond primates, and a few other mammals, to mice, affording the opportunity to exploit genetically diverse mouse panels to model the broad spectrum of responses to infection in patient populations. Here we surveyed responses to VOC infection in genetically diverse Collaborative Cross (CC) founder strains. Infection of wild-derived CC founder strains produced a broad range of viral burden, disease susceptibility and survival, whereas most other strains were resistant to disease despite measurable lung viral titers. In particular, CAST/EiJ, a wild-derived strain, developed high lung viral burdens, more severe lung pathology than seen in other CC strains, and a dysregulated cytokine profile resulting in morbidity and mortality. These inbred mouse strains may serve as a valuable platform to evaluate therapeutic countermeasures against severe COVID-19 and other coronavirus pandemics in the future.
Authors
- Tricia Hart (ORCID: https://orcid.org/0000-0002-7999-3994)
- William W. Reiley (ORCID: https://orcid.org/0000-0001-6383-8343)
- Mike Tighe
- Frank M. Szaba (ORCID: https://orcid.org/0000-0002-7305-083X)
- Larry Kummer
- Sean Casey
- Mark D. Adams (ORCID: https://orcid.org/0000-0003-3161-7460)
- Cathleen M. Lutz (ORCID: https://orcid.org/0000-0003-2502-1900)
- Nadia Rosenthal (ORCID: https://orcid.org/0000-0002-7599-7365)
- Kathleen G. Lanzer (ORCID: https://orcid.org/0000-0002-3315-8547)
- Kelsey L. Travis (ORCID: https://orcid.org/0000-0002-3370-4819)
- Isaac Lowthian Bell (ORCID: https://orcid.org/0000-0002-6641-2281)
- Tres Cookenham (ORCID: https://orcid.org/0000-0002-1066-5036)
- Naga Rama Kothapalli (ORCID: https://orcid.org/0000-0001-7993-8525)
- Candice N. Baker (ORCID: https://orcid.org/0009-0008-7793-3008)
- Jerrold M. Ward (ORCID: https://orcid.org/0000-0002-6350-8982)
- Olivia Bedard (ORCID: https://orcid.org/0009-0008-7888-1895)
- Purva Vats
- Shelton S. Bradrick (ORCID: https://orcid.org/0000-0003-1566-9797)
- Priya Shanbhag
- Natalie Oberding
- Janine Hvizdos (ORCID: https://orcid.org/0009-0004-0054-8671)
- Jeffrey M. Harder (ORCID: https://orcid.org/0000-0003-3832-3553)
- Debra K. Duso
Institutions
- Trudeau Institute (US)
- Lung Institute (US)
- Jackson Laboratory (US)
- Imperial College London (GB)
Publication Details
- Journal
- Scientific Reports
- Published
- 2024-10-24
- DOI
- https://doi.org/10.1038/s41598-024-77087-1
- Citations
- 3
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 1.38
Funders
- F. M. Kirby Foundation
- James N. Kirby Foundation
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases