Publisher Correction: SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function

Autor: James T. Earnest, Julie M. Fox, Jon H. Ritter, Rita E. Chen, Natasha M. Kafai, Richard D. Head, Annette Robichaud, Broc T. McCune, Adam L. Bailey, Sarah Dort, Michael J. Holtzman, Shamus P. Keeler, Emma S. Winkler, Liang I. Kang, Michael S. Diamond, Jinsheng Yu, Sharmila Nair
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Genetically modified mouse
2019-20 coronavirus outbreak
Coronavirus disease 2019 (COVID-19)
Neutrophils
T-Lymphocytes
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Pneumonia
Viral
Immunology
Mice
Transgenic
Inflammation
Peptidyl-Dipeptidase A
Lymphocyte Activation
Virus Replication
Monocytes
Betacoronavirus
Interferon-gamma
Mice
Chlorocebus aethiops
Leukocytes
medicine
Animals
Humans
Immunology and Allergy
Promoter Regions
Genetic
Pandemics
Vero Cells
Lung
Keratin-18
SARS-CoV-2
business.industry
NF-kappa B
COVID-19
Antimicrobial responses
Pneumonia
Publisher Correction
Virology
Immunity
Innate
Disease Models
Animal
medicine.anatomical_structure
Neutrophil Infiltration
Interferon Type I
Female
Angiotensin-Converting Enzyme 2
medicine.symptom
Coronavirus Infections
business
Function (biology)
Zdroj: Nature Immunology
ISSN: 1529-2916
1529-2908
DOI: 10.1038/s41590-020-0794-2
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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