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

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 pre...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e5eb566b6b03413b9f2ac96acfa86144
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e5eb566b6b03413b9f2ac96acfa86144
record_format	dspace
spelling	oai:doaj.org-article:e5eb566b6b03413b9f2ac96acfa861442021-12-02T16:26:38ZHigh-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro10.1038/s41598-021-94095-72045-2322https://doaj.org/article/e5eb566b6b03413b9f2ac96acfa861442021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94095-7https://doaj.org/toc/2045-2322Abstract 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.A. L. GardR. J. LuuC. R. MillerR. MaloneyB. P. CainE. E. MarrD. M. BurnsR. GaiblerT. J. MulhernC. A. WongJ. AlladinaJ. R. CoppetaP. LiuJ. P. WangH. AzizgolshaniR. Fennell FezzieJ. L. BalestriniB. C. IsenbergB. D. MedoffR. W. FinbergJ. T. BorensteinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro
description	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.
format	article
author	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
author_facet	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
author_sort	A. L. Gard
title	High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro
title_short	High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro
title_full	High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro
title_fullStr	High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro
title_full_unstemmed	High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro
title_sort	high-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e5eb566b6b03413b9f2ac96acfa86144
work_keys_str_mv	AT algard highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT rjluu highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT crmiller highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT rmaloney highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT bpcain highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT eemarr highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT dmburns highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT rgaibler highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT tjmulhern highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT cawong highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT jalladina highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT jrcoppeta highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT pliu highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT jpwang highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT hazizgolshani highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT rfennellfezzie highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT jlbalestrini highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT bcisenberg highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT bdmedoff highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT rwfinberg highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro AT jtborenstein highthroughputhumanprimarycellbasedairwaymodelforevaluatinginfluenzacoronavirusorotherrespiratoryvirusesinvitro
_version_	1718384024245764096

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

Ejemplares similares