دورية أكاديمية
Generation of a lethal mouse model expressing human ACE2 and TMPRSS2 for SARS-CoV-2 infection and pathogenesis
| العنوان: | Generation of a lethal mouse model expressing human ACE2 and TMPRSS2 for SARS-CoV-2 infection and pathogenesis |
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| المؤلفون: | Gi Uk Jeong, Insu Hwang, Wooseong Lee, Ji Hyun Choi, Gun Young Yoon, Hae Soo Kim, Jeong-Sun Yang, Kyung-Chang Kim, Joo-Yeon Lee, Seong-Jun Kim, Young-Chan Kwon, Kyun-Do Kim |
| المصدر: | Experimental and Molecular Medicine, Vol 56, Iss 5, Pp 1221-1229 (2024) |
| بيانات النشر: | Nature Publishing Group, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Biochemistry |
| مصطلحات موضوعية: | Medicine, Biochemistry, QD415-436 |
| الوصف: | Abstract Mouse models expressing human ACE2 for coronavirus disease 2019 have been frequently used to understand its pathogenesis and develop therapeutic strategies against SARS-CoV-2. Given that human TMPRSS2 supports viral entry, replication, and pathogenesis, we established a double-transgenic mouse model expressing both human ACE2 and TMPRSS2 for SARS-CoV-2 infection. Co-overexpression of both genes increased viral infectivity in vitro and in vivo. Double-transgenic mice showed significant body weight loss, clinical disease symptoms, acute lung injury, lung inflammation, and lethality in response to viral infection, indicating that they were highly susceptible to SARS-CoV-2. Pretreatment with the TMPRSS2 inhibitor, nafamostat, effectively reduced virus-induced weight loss, viral replication, and mortality in the double-transgenic mice. Moreover, the susceptibility and differential pathogenesis of SARS-CoV-2 variants were demonstrated in this animal model. Together, our results demonstrate that double-transgenic mice could provide a highly susceptible mouse model for viral infection to understand SARS-CoV-2 pathogenesis and evaluate antiviral therapeutics against coronavirus disease 2019. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2092-6413 |
| العلاقة: | https://doaj.org/toc/2092-6413Test |
| DOI: | 10.1038/s12276-024-01197-z |
| الوصول الحر: | https://doaj.org/article/0bfcda8eddce4df68827b69061b602d5Test |
| رقم الانضمام: | edsdoj.0bfcda8eddce4df68827b69061b602d5 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20926413 |
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| DOI: | 10.1038/s12276-024-01197-z |