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
in English
| MEDLINE | ID: covidwho-728991
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia
/
Pneumonia, Viral
/
Coronavirus Infections
/
Peptidyl-Dipeptidase A
/
Betacoronavirus
/
Immunity, Innate
Type of study:
Experimental Studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Journal:
Nat Immunol
Journal subject:
Allergy and Immunology
Year:
2020
Document Type:
Article
Affiliation country:
S41590-020-0778-2
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