SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function.
Nat Immunol
; 21(11): 1327-1335, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32839612
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
/
Pneumonia Viral
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Infecções por Coronavirus
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Peptidil Dipeptidase A
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Betacoronavirus
/
Imunidade Inata
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
/
Female
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Humans
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Male
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos