Nature Communications (Jul 2023)
Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19
- Shelly J. Robertson,
- Olivia Bedard,
- Kristin L. McNally,
- Carl Shaia,
- Chad S. Clancy,
- Matthew Lewis,
- Rebecca M. Broeckel,
- Abhilash I. Chiramel,
- Jeffrey G. Shannon,
- Gail L. Sturdevant,
- Rebecca Rosenke,
- Sarah L. Anzick,
- Elvira Forte,
- Christoph Preuss,
- Candice N. Baker,
- Jeffrey M. Harder,
- Catherine Brunton,
- Steven Munger,
- Daniel P. Bruno,
- Justin B. Lack,
- Jacqueline M. Leung,
- Amirhossein Shamsaddini,
- Paul Gardina,
- Daniel E. Sturdevant,
- Jian Sun,
- Craig Martens,
- Steven M. Holland,
- Nadia A. Rosenthal,
- Sonja M. Best
Affiliations
- Shelly J. Robertson
- Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH
- Olivia Bedard
- The Jackson Laboratory
- Kristin L. McNally
- Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH
- Carl Shaia
- Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH
- Chad S. Clancy
- Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH
- Matthew Lewis
- Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH
- Rebecca M. Broeckel
- Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH
- Abhilash I. Chiramel
- Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH
- Jeffrey G. Shannon
- Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH
- Gail L. Sturdevant
- Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH
- Rebecca Rosenke
- Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH
- Sarah L. Anzick
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, NIH
- Elvira Forte
- The Jackson Laboratory
- Christoph Preuss
- The Jackson Laboratory
- Candice N. Baker
- The Jackson Laboratory
- Jeffrey M. Harder
- The Jackson Laboratory
- Catherine Brunton
- The Jackson Laboratory
- Steven Munger
- The Jackson Laboratory
- Daniel P. Bruno
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, NIH
- Justin B. Lack
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, NIH
- Jacqueline M. Leung
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, NIH
- Amirhossein Shamsaddini
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, NIH
- Paul Gardina
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, NIH
- Daniel E. Sturdevant
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, NIH
- Jian Sun
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, NIH
- Craig Martens
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, NIH
- Steven M. Holland
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH
- Nadia A. Rosenthal
- The Jackson Laboratory
- Sonja M. Best
- Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH
- DOI
- https://doi.org/10.1038/s41467-023-40076-5
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 13
Abstract
Abstract 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.
