UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

2021-07-22

Document Type

Article

Disciplines

Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Immunotherapy | Infectious Disease | Influenza Humans | Respiratory Tract Diseases | Virology | Virus Diseases

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.

Keywords

respiratory viruses, influenza, coronvairus

Rights and Permissions

Copyright © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

DOI of Published Version

10.1038/s41598-021-94095-7

Source

Gard AL, Luu RJ, Miller CR, Maloney R, Cain BP, Marr EE, Burns DM, Gaibler R, Mulhern TJ, Wong CA, Alladina J, Coppeta JR, Liu P, Wang JP, Azizgolshani H, Fezzie RF, Balestrini JL, Isenberg BC, Medoff BD, Finberg RW, Borenstein JT. High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro. Sci Rep. 2021 Jul 22;11(1):14961. doi: 10.1038/s41598-021-94095-7. PMID: 34294757; PMCID: PMC8298517. Link to article on publisher's site

Journal/Book/Conference Title

Scientific reports

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

34294757

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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