Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19
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Published:2023-07-25
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Robertson Shelly J., Bedard Olivia, McNally Kristin L., Shaia CarlORCID, Clancy Chad S.ORCID, Lewis Matthew, Broeckel Rebecca M., Chiramel Abhilash I., Shannon Jeffrey G.ORCID, Sturdevant Gail L., Rosenke Rebecca, Anzick Sarah L., Forte Elvira, Preuss Christoph, Baker Candice N.ORCID, Harder Jeffrey M., Brunton Catherine, Munger StevenORCID, Bruno Daniel P., Lack Justin B., Leung Jacqueline M.ORCID, Shamsaddini Amirhossein, Gardina Paul, Sturdevant Daniel E., Sun Jian, Martens Craig, Holland Steven M., Rosenthal Nadia A.ORCID, Best Sonja M.ORCID
Abstract
AbstractInflammation 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.
Funder
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference57 articles.
1. Richardson, S. et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 323, 2052–2059 (2020). 2. Long, Q. X. et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat. Med. 26, 1200–1204 (2020). 3. Zhang, Q. et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 370, eabd4570 (2020). 4. Mainous, A. G., Rooks, B. J., Wu, V. & Orlando, F. A. COVID-19 post-acute sequelae among adults: 12 month mortality risk. Front. Med. 8, 778434 (2021). 5. Docherty, A. B. et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ 369, m1985 (2020).
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