SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function
| Autor: | Broc T. McCune, Annette Robichaud, Shamus P. Keeler, Natasha M. Kafai, Adam L. Bailey, Richard D. Head, Julie M. Fox, Sharmila Nair, Jinsheng Yu, Michael S. Diamond, Rita E. Chen, Liang I. Kang, James T. Earnest, Sarah Dort, Michael J. Holtzman, Jon H. Ritter, Emma S. Winkler |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Genetically modified mouse viruses Immunology Inflammation macromolecular substances Article Pulmonary function testing 03 medical and health sciences 0302 clinical medicine Immune system Interferon medicine Immunology and Allergy Receptor Innate immune system Lung business.industry respiratory system respiratory tract diseases 030104 developmental biology medicine.anatomical_structure medicine.symptom business 030215 immunology medicine.drug |
| Zdroj: | Nature Immunology Nature immunology |
| ISSN: | 1529-2916 1529-2908 |
| Popis: | Although animal models have been evaluated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, none have fully recapitulated the lung disease phenotypes seen in humans who have been hospitalized. Here, we evaluate transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2) as a model of SARS-CoV-2 infection. Intranasal inoculation of SARS-CoV-2 in K18-hACE2 mice results in high levels of viral infection in lungs, with spread to other organs. A decline in pulmonary function occurs 4 days after peak viral titer and correlates with infiltration of monocytes, neutrophils and activated T cells. SARS-CoV-2-infected lung tissues show a massively upregulated innate immune response with signatures of nuclear factor-κB-dependent, type I and II interferon signaling, and leukocyte activation pathways. Thus, the K18-hACE2 model of SARS-CoV-2 infection shares many features of severe COVID-19 infection and can be used to define the basis of lung disease and test immune and antiviral-based countermeasures. |
| Databáze: | OpenAIRE |
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