Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice
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Published:2020-11-30
Issue:1
Volume:11
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:
Oladunni Fatai S.ORCID, Park Jun-GyuORCID, Pino Paula A., Gonzalez Olga, Akhter Anwari, Allué-Guardia Anna, Olmo-Fontánez Angélica, Gautam Shalini, Garcia-Vilanova AndreuORCID, Ye Chengjin, Chiem Kevin, Headley ColwynORCID, Dwivedi Varun, Parodi Laura M., Alfson Kendra J., Staples Hilary M., Schami Alyssa, Garcia Juan I., Whigham Alison, Platt Roy Neal, Gazi Michal, Martinez Jesse, Chuba Colin, Earley Stephanie, Rodriguez Oscar H., Mdaki Stephanie Davis, Kavelish Katrina N., Escalona Renee, Hallam Cory R. A., Christie Corbett, Patterson Jean L.ORCID, Anderson Tim J. C., Carrion RicardoORCID, Dick Edward J.ORCID, Hall-Ursone Shannan, Schlesinger Larry S., Alvarez Xavier, Kaushal DeepakORCID, Giavedoni Luis D., Turner JoanneORCID, Martinez-Sobrido LuisORCID, Torrelles Jordi B.ORCID
Abstract
AbstractVaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.
Funder
Texas Biomedical Research Institute Philanthropic Funds for COVID-19 Research
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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