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SARS-CoV-2 infection in the lungs of human ACE2 transgenic mice causes severe inflammation, immune cell infiltration, and compromised respiratory function.
bioRxiv ; 2020 Jul 10.
Article in English | MEDLINE | ID: covidwho-665969
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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Semantic information from SemMedBD (by NLM)
1. Lung PART_OF Mic
Subject
Lung
Predicate
PART_OF
Object
Mic
2. Lung LOCATION_OF Severe Acute Respiratory Syndrome
Subject
Lung
Predicate
LOCATION_OF
Object
Severe Acute Respiratory Syndrome
3. 2019 novel coronavirus CAUSES COVID-19
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
COVID-19
4. ACE2 gene|ACE2 PART_OF Homo sapiens
Subject
ACE2 gene|ACE2
Predicate
PART_OF
Object
Homo sapiens
5. KRT18 gene|KRT18 STIMULATES ACE2 gene|ACE2
Subject
KRT18 gene|KRT18
Predicate
STIMULATES
Object
ACE2 gene|ACE2
6. 2019 novel coronavirus PROCESS_OF Mus
Subject
2019 novel coronavirus
Predicate
PROCESS_OF
Object
Mus
7. Structure of parenchyma of lung LOCATION_OF Virus Diseases
Subject
Structure of parenchyma of lung
Predicate
LOCATION_OF
Object
Virus Diseases
8. Infiltration CAUSES Pneumonia
Subject
Infiltration
Predicate
CAUSES
Object
Pneumonia
9. Structure of parenchyma of lung LOCATION_OF Sequence Analysis
Subject
Structure of parenchyma of lung
Predicate
LOCATION_OF
Object
Sequence Analysis
10. Severe infection PROCESS_OF Homo sapiens
Subject
Severe infection
Predicate
PROCESS_OF
Object
Homo sapiens
11. Lung PART_OF Mice, Transgenic
Subject
Lung
Predicate
PART_OF
Object
Mice, Transgenic
12. Lung LOCATION_OF Severe Acute Respiratory Syndrome
Subject
Lung
Predicate
LOCATION_OF
Object
Severe Acute Respiratory Syndrome
13. 2019 novel coronavirus CAUSES COVID-19
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
COVID-19
14. ACE2 gene|ACE2 PART_OF Homo sapiens
Subject
ACE2 gene|ACE2
Predicate
PART_OF
Object
Homo sapiens
15. KRT18 gene|KRT18 STIMULATES ACE2 gene|ACE2
Subject
KRT18 gene|KRT18
Predicate
STIMULATES
Object
ACE2 gene|ACE2
16. 2019 novel coronavirus PROCESS_OF Mus
Subject
2019 novel coronavirus
Predicate
PROCESS_OF
Object
Mus
17. Structure of parenchyma of lung LOCATION_OF Virus Diseases
Subject
Structure of parenchyma of lung
Predicate
LOCATION_OF
Object
Virus Diseases
18. Infiltration CAUSES Pneumonia
Subject
Infiltration
Predicate
CAUSES
Object
Pneumonia
19. Structure of parenchyma of lung LOCATION_OF Sequence Analysis
Subject
Structure of parenchyma of lung
Predicate
LOCATION_OF
Object
Sequence Analysis
20. Severe infection PROCESS_OF Homo sapiens
Subject
Severe infection
Predicate
PROCESS_OF
Object
Homo sapiens
ABSTRACT
Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) emerged in late 2019 and has spread worldwide resulting in the Coronavirus Disease 2019 (COVID-19) pandemic. Although animal models have been evaluated for SARS-CoV-2 infection, none have recapitulated the severe lung disease phenotypes seen in hospitalized human cases. Here, we evaluate heterozygous transgenic mice expressing the human ACE2 receptor driven by the epithelial cell cytokeratin-18 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 lung tissues with additional spread to other organs. Remarkably, a decline in pulmonary function, as measured by static and dynamic tests of respiratory capacity, occurs 4 days after peak viral titer and correlates with an inflammatory response marked by infiltration into the lung of monocytes, neutrophils, and activated T cells resulting in pneumonia. Cytokine profiling and RNA sequencing analysis of SARS-CoV-2-infected lung tissues show a massively upregulated innate immune response with prominent signatures of NF-kB-dependent, type I and II interferon signaling, and leukocyte activation pathways. Thus, the K18-hACE2 model of SARS-CoV-2 infection recapitulates many features of severe COVID-19 infection in humans and can be used to define the mechanistic basis of lung disease and test immune and antiviral-based countermeasures.

Full text: Available Collection: International databases Database: MEDLINE Type of study: Etiology study Language: English Year: 2020 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Etiology study Language: English Year: 2020 Document Type: Article