Academic Journal
High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro
| العنوان: | High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro |
|---|---|
| المؤلفون: | A. L. Gard, R. J. Luu, C. R. Miller, R. Maloney, B. P. Cain, E. E. Marr, D. M. Burns, R. Gaibler, T. J. Mulhern, C. A. Wong, J. Alladina, J. R. Coppeta, P. Liu, J. P. Wang, H. Azizgolshani, R. Fennell Fezzie, J. L. Balestrini, B. C. Isenberg, B. D. Medoff, R. W. Finberg, J. T. Borenstein |
| المصدر: | Scientific Reports, Vol 11, Iss 1, Pp 1-18 (2021) |
| بيانات النشر: | Nature Portfolio |
| سنة النشر: | 2021 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Influenza and other respiratory viruses present a significant threat to public health, national security, and the world economy, and can lead to the emergence of global pandemics such as from COVID-19. A barrier to the development of effective therapeutics is the absence of a robust and predictive preclinical model, with most studies relying on a combination of in vitro screening with immortalized cell lines and low-throughput animal models. Here, we integrate human primary airway epithelial cells into a custom-engineered 96-device platform (PREDICT96-ALI) in which tissues are cultured in an array of microchannel-based culture chambers at an air–liquid interface, in a configuration compatible with high resolution in-situ imaging and real-time sensing. We apply this platform to influenza A virus and coronavirus infections, evaluating viral infection kinetics and antiviral agent dosing across multiple strains and donor populations of human primary cells. Human coronaviruses HCoV-NL63 and SARS-CoV-2 enter host cells via ACE2 and utilize the protease TMPRSS2 for spike protein priming, and we confirm their expression, demonstrate infection across a range of multiplicities of infection, and evaluate the efficacy of camostat mesylate, a known inhibitor of HCoV-NL63 infection. This new capability can be used to address a major gap in the rapid assessment of therapeutic efficacy of small molecules and antiviral agents against influenza and other respiratory viruses including coronaviruses. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doi.org/10.1038/s41598-021-94095-7; https://doaj.org/toc/2045-2322; https://doaj.org/article/e5eb566b6b03413b9f2ac96acfa86144 |
| DOI: | 10.1038/s41598-021-94095-7 |
| الاتاحة: | https://doi.org/10.1038/s41598-021-94095-7 https://doaj.org/article/e5eb566b6b03413b9f2ac96acfa86144 |
| رقم الانضمام: | edsbas.67D8C980 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20452322 |
|---|---|
| DOI: | 10.1038/s41598-021-94095-7 |