TY - JOUR
KW - Biomedical Engineering
KW - Viral infection
AU - A. L. Gard
AU - R. J. Luu
AU - C. R. Miller
AU - R. Maloney
AU - B. P. Cain
AU - E. E. Marr
AU - D. M. Burns
AU - R. Gaibler
AU - T. J. Mulhern
AU - C. A. Wong
AU - J. Alladina
AU - J. R. Coppeta
AU - P. Liu
AU - J. P. Wang
AU - H. Azizgolshani
AU - R. Fennell Fezzie
AU - J. L. Balestrini
AU - B. C. Isenberg
AU - B. D. Medoff
AU - R. W. Finberg
AU - J. T. Borenstein
AB - 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.
BT - Scientific Reports
DA - 2021-07-22
DO - 10.1038/s41598-021-94095-7
IS - 1
LA - en
N2 - 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.
PY - 2021
EP - 14961
T2 - Scientific Reports
TI - High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro
UR - https://www.nature.com/articles/s41598-021-94095-7
VL - 11
Y2 - 2023-08-09
SN - 2045-2322
ER -