Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease
| العنوان: | Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease |
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| المؤلفون: | Joshua D. Shamblin, Eric M. Mucker, Brian D. Carey, Aura R. Garrison, Hypaitia B. Rauch, Jay W. Hooper, Xiankun Zeng, Jeffrey M. Smith, Bradley S. Hollidge, April M. Babka, Collin Fitzpatrick, Rebecca L. Brocato, Curtis R. Cline, Catherine V. Badger, Jun Liu, Lauren E. White, Joseph W. Golden |
| المصدر: | JCI Insight, Vol 5, Iss 19 (2020) JCI Insight |
| بيانات النشر: | American Society for Clinical investigation, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Genetically modified mouse, Pneumonia, Viral, Mice, Transgenic, Disease, Peptidyl-Dipeptidase A, Lung injury, Mouse models, Severe Acute Respiratory Syndrome, Virus Replication, Severity of Illness Index, Keratin 18, Proinflammatory cytokine, Pathogenesis, Mice, 03 medical and health sciences, 0302 clinical medicine, Cause of Death, medicine, Animals, Humans, Lung, Pandemics, Molecular pathology, Infectious disease, business.industry, Respiratory disease, COVID-19, General Medicine, respiratory system, medicine.disease, respiratory tract diseases, Survival Rate, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, Angiotensin-converting enzyme 2, Disease Progression, Medicine, Female, Angiotensin-Converting Enzyme 2, Coronavirus Infections, business, Research Article |
| الوصف: | The emergence of SARS-CoV-2 has created an international health crisis, and small animal models mirroring SARS-CoV-2 human disease are essential for medical countermeasure (MCM) development. Mice are refractory to SARS-CoV-2 infection owing to low-affinity binding to the murine angiotensin-converting enzyme 2 (ACE2) protein. Here, we evaluated the pathogenesis of SARS-CoV-2 in male and female mice expressing the human ACE2 gene under the control of the keratin 18 promoter (K18). In contrast to nontransgenic mice, intranasal exposure of K18-hACE2 animals to 2 different doses of SARS-CoV-2 resulted in acute disease, including weight loss, lung injury, brain infection, and lethality. Vasculitis was the most prominent finding in the lungs of infected mice. Transcriptomic analysis from lungs of infected animals showed increases in transcripts involved in lung injury and inflammatory cytokines. In the low-dose challenge groups, there was a survival advantage in the female mice, with 60% surviving infection, whereas all male mice succumbed to disease. Male mice that succumbed to disease had higher levels of inflammatory transcripts compared with female mice. To our knowledge, this is the first highly lethal murine infection model for SARS-CoV-2 and should be valuable for the study of SARS-CoV-2 pathogenesis and for the assessment of MCMs. A highly lethal murine infection model for SARS-CoV-2 using mice transgenic for the human ACE2 protein is described. |
| اللغة: | English |
| تدمد: | 2379-3708 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e231945a434fa0e68ce0e1a1c6723d30 https://doaj.org/article/2c20d6ee5a6a43d886df68b98fd87586 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e231945a434fa0e68ce0e1a1c6723d30 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23793708 |
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