Characterization of Collaborative Cross mouse founder strain CAST/EiJ as a novel model for lethal COVID-19
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View abstract on PubMed
Summary
This summary is machine-generated.SARS-CoV-2 variants of concern (VOCs) infect mice, enabling studies of diverse COVID-19 responses. Specific mouse strains, like CAST/EiJ, show severe disease and may model human responses for therapeutic development.
Area Of Science
- Virology
- Immunology
- Genetics
Background
- Mutations in SARS-CoV-2 variants of concern (VOCs) have expanded the virus's host range to include mice.
- Genetically diverse mouse models are needed to understand the varied responses to SARS-CoV-2 infection observed in human populations.
Purpose Of The Study
- To survey the responses to VOC infection in genetically diverse Collaborative Cross (CC) founder strains.
- To identify mouse models that can effectively replicate the spectrum of human COVID-19 disease.
Main Methods
- Infection of wild-derived Collaborative Cross (CC) founder strains with SARS-CoV-2 VOCs.
- Assessment of viral burden, lung pathology, cytokine profiles, disease susceptibility, and survival.
- Comparison of responses across different inbred mouse strains.
Main Results
- Collaborative Cross (CC) founder strains exhibited a wide range of viral loads, disease severity, and survival rates.
- Most strains were resistant to severe disease, despite detectable lung viral titers.
- The CAST/EiJ strain developed high lung viral burdens, severe lung pathology, and a dysregulated cytokine response, leading to morbidity and mortality.
Conclusions
- Genetically diverse mouse strains, particularly CAST/EiJ, provide valuable models for studying SARS-CoV-2 pathogenesis.
- These models can be used to evaluate therapeutic countermeasures against severe COVID-19 and future coronavirus pandemics.
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