High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro

Autor: 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
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Scientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-021-94095-7
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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