tetano
Editor, Senior Moderator
Nat Commun
. 2023 Jul 25;14(1):4481.
doi: 10.1038/s41467-023-40076-5. 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[SUP] 1 2 [/SUP], Olivia Bedard[SUP] 3 [/SUP], Kristin L McNally[SUP] 1 [/SUP], Carl Shaia[SUP] 4 [/SUP], Chad S Clancy[SUP] 4 [/SUP], Matthew Lewis[SUP] 1 [/SUP], Rebecca M Broeckel[SUP] 1 [/SUP], Abhilash I Chiramel[SUP] 1 [/SUP], Jeffrey G Shannon[SUP] 2 [/SUP], Gail L Sturdevant[SUP] 1 2 [/SUP], Rebecca Rosenke[SUP] 4 [/SUP], Sarah L Anzick[SUP] 5 [/SUP], Elvira Forte[SUP] 3 6 [/SUP], Christoph Preuss[SUP] 3 [/SUP], Candice N Baker[SUP] 3 [/SUP], Jeffrey M Harder[SUP] 3 [/SUP], Catherine Brunton[SUP] 3 [/SUP], Steven Munger[SUP] 3 [/SUP], Daniel P Bruno[SUP] 5 [/SUP], Justin B Lack[SUP] 5 [/SUP], Jacqueline M Leung[SUP] 5 [/SUP], Amirhossein Shamsaddini[SUP] 5 [/SUP], Paul Gardina[SUP] 5 [/SUP], Daniel E Sturdevant[SUP] 5 [/SUP], Jian Sun[SUP] 5 [/SUP], Craig Martens[SUP] 5 [/SUP], Steven M Holland[SUP] 7 [/SUP], Nadia A Rosenthal[SUP] 8 9 [/SUP], Sonja M Best[SUP] 10 11 [/SUP]
Affiliations
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.
. 2023 Jul 25;14(1):4481.
doi: 10.1038/s41467-023-40076-5. 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[SUP] 1 2 [/SUP], Olivia Bedard[SUP] 3 [/SUP], Kristin L McNally[SUP] 1 [/SUP], Carl Shaia[SUP] 4 [/SUP], Chad S Clancy[SUP] 4 [/SUP], Matthew Lewis[SUP] 1 [/SUP], Rebecca M Broeckel[SUP] 1 [/SUP], Abhilash I Chiramel[SUP] 1 [/SUP], Jeffrey G Shannon[SUP] 2 [/SUP], Gail L Sturdevant[SUP] 1 2 [/SUP], Rebecca Rosenke[SUP] 4 [/SUP], Sarah L Anzick[SUP] 5 [/SUP], Elvira Forte[SUP] 3 6 [/SUP], Christoph Preuss[SUP] 3 [/SUP], Candice N Baker[SUP] 3 [/SUP], Jeffrey M Harder[SUP] 3 [/SUP], Catherine Brunton[SUP] 3 [/SUP], Steven Munger[SUP] 3 [/SUP], Daniel P Bruno[SUP] 5 [/SUP], Justin B Lack[SUP] 5 [/SUP], Jacqueline M Leung[SUP] 5 [/SUP], Amirhossein Shamsaddini[SUP] 5 [/SUP], Paul Gardina[SUP] 5 [/SUP], Daniel E Sturdevant[SUP] 5 [/SUP], Jian Sun[SUP] 5 [/SUP], Craig Martens[SUP] 5 [/SUP], Steven M Holland[SUP] 7 [/SUP], Nadia A Rosenthal[SUP] 8 9 [/SUP], Sonja M Best[SUP] 10 11 [/SUP]
Affiliations
- PMID: 37491352
- DOI: 10.1038/s41467-023-40076-5
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.