Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19

Inflammation in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection drives severity of coronavirus disease 2019 (COVID-19) and is influenced by host genetics. To understand mechanisms of inflammation, animal models that reflect genetic diversity and clinical outcomes o...

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Detalles Bibliográficos
Autores principales: Robertson, Shelly J., Bedard, Olivia, McNally, Kristin L., Shaia, Carl, Clancy, Chad S., Lewis, Matthew, Broeckel, Rebecca M., Chiramel, Abhilash I., Shannon, Jeffrey G., Sturdevant, Gail L., Rosenke, Rebecca, Anzick, Sarah L., Forte, Elvira, Preuss, Christoph, Baker, Candice N., Harder, Jeffrey M., Brunton, Catherine, Munger, Steven, Bruno, Daniel P., Lack, Justin B., Leung, Jacqueline M., Shamsaddini, Amirhossein, Gardina, Paul, Sturdevant, Daniel E., Sun, Jian, Martens, Craig, Holland, Steven M., Rosenthal, Nadia A., Best, Sonja M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10368652/
https://www.ncbi.nlm.nih.gov/pubmed/37491352
http://dx.doi.org/10.1038/s41467-023-40076-5
Descripción
Sumario:Inflammation in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection drives severity of coronavirus disease 2019 (COVID-19) and is influenced by host genetics. To understand mechanisms of inflammation, animal models that reflect genetic diversity and clinical outcomes observed in humans are needed. We report a mouse panel comprising the genetically diverse Collaborative Cross (CC) founder strains crossed to human ACE2 transgenic mice (K18-hACE2) that confers susceptibility to SARS-CoV-2. Infection of CC x K18-hACE2 resulted in a spectrum of survival, viral replication kinetics, and immune profiles. Importantly, in contrast to the K18-hACE2 model, early type I interferon (IFN-I) and regulated proinflammatory responses were required for control of SARS-CoV-2 replication in PWK x K18-hACE2 mice that were highly resistant to disease. Thus, virus dynamics and inflammation observed in COVID-19 can be modeled in diverse mouse strains that provide a genetically tractable platform for understanding anti-coronavirus immunity.

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