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

Authors :
Robertson S
Bedard O
McNally K
Shaia C
Clancy C
Lewis M
Broeckel R
Chiramel A
Shannon JG
Sturdevant G
Rosenke R
Anzick SL
Forte E
Preuss C
Baker C
Harder J
Brunton C
Munger SC
Bruno DP
Lack JB
Leung JM
Shamsaddini A
Gardina P
Sturdevant D
Sun J
Martens C
Holland S
Rosenthal N
Best S
Source :
BioRxiv : the preprint server for biology [bioRxiv] 2023 Apr 21. Date of Electronic Publication: 2023 Apr 21.
Publication Year :
2023

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.

Details

Language :
English
Database :
MEDLINE
Journal :
BioRxiv : the preprint server for biology
Accession number :
35233576
Full Text :
https://doi.org/10.1101/2021.09.17.460664