Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2

التفاصيل البيبلوغرافية
العنوان: Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2
المؤلفون: Wei Zhang, Yan Zhu, Xu Rui Shen, Peng Zhou, Lei Zhang, Hao Rui Si, Ralph S. Baric, Li Qian, Yi Wu Zhou, Ren Di Jiang, Bei Li, Mei Qin Liu, Juan Min, Zhengli Shi, Xing-Lou Yang, Chao Shan, Xi Wang, Hua Jun Zhang, Qi Wang, Ying Chen
المصدر: Cell
بيانات النشر: The University of North Carolina at Chapel Hill University Libraries, 2020.
سنة النشر: 2020
مصطلحات موضوعية: Genetically modified mouse, Male, viruses, Pneumonia, Viral, Mice, Transgenic, Biology, Peptidyl-Dipeptidase A, medicine.disease_cause, Article, Virus, General Biochemistry, Genetics and Molecular Biology, human ACE2 transgenic mouse, Pathogenesis, 03 medical and health sciences, Betacoronavirus, Mice, 0302 clinical medicine, Weight Loss, medicine, pneumonia, Animals, Humans, Pandemics, 030304 developmental biology, Coronavirus, 0303 health sciences, Mice, Inbred C3H, Innate immune system, SARS-CoV-2, COVID-19, medicine.disease, Virology, respiratory tract diseases, Mice, Inbred C57BL, Pneumonia, Disease Models, Animal, Viral Tropism, Angiotensin-converting enzyme 2, Tissue tropism, Female, Angiotensin-Converting Enzyme 2, Coronavirus Infections, Lung Diseases, Interstitial, 030217 neurology & neurosurgery
الوصف: Summary COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human angiotensin-converting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Lastly, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics.
Highlights • SARS-CoV-2 could infect HFH4-hACE2 mice and cause death. • SARS-CoV-2 infection localizes to lungs of mice and causes typical interstitial pneumonia. • Pre-exposure to SARS-CoV-2 protects mice from lethal challenge.
A SARS-CoV-2 hACE2 transgenic mouse infection model recapitulates a number of infection symptoms and pathology in COVID-19 patients. Pre-exposure to SARS-CoV-2 was able to protect mice from severe pneumonia.
اللغة: English
DOI: 10.17615/8tnm-fc73
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5dffbd33e92bd1c7c4b032f5d8b8ae50
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....5dffbd33e92bd1c7c4b032f5d8b8ae50
قاعدة البيانات: OpenAIRE