Impact of changes in human airway epithelial cellular composition and differentiation on SARS-CoV-2 infection biology.

Thaler, M; Wang, Y; van der Does, AM; Faiz, A; Ninaber, DK; Ogando, NS; Beckert, H; Taube, C; Salgado-Benvindo, C; Snijder, EJ; Bredenbeek, PJ; Hiemstra, PS; van Hemert, MJ

Impact of changes in human airway epithelial cellular composition and differentiation on SARS-CoV-2 infection biology.

Thaler, M Wang, Y van der Does, AM Faiz, A

Ninaber, DK Ogando, NS Beckert, H Taube, C Salgado-Benvindo, C Snijder, EJ Bredenbeek, PJ Hiemstra, PS van Hemert, MJ

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Publisher:: Karger Publishers
Publication Type:: Journal Article
Citation:: J Innate Immun, 2023, 15, (1), pp. 562-580
Issue Date:: 2023-03-25

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Field	Value	Language
dc.contributor.author	Thaler, M
dc.contributor.author	Wang, Y
dc.contributor.author	van der Does, AM
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538
dc.contributor.author	Ninaber, DK
dc.contributor.author	Ogando, NS
dc.contributor.author	Beckert, H
dc.contributor.author	Taube, C
dc.contributor.author	Salgado-Benvindo, C
dc.contributor.author	Snijder, EJ
dc.contributor.author	Bredenbeek, PJ
dc.contributor.author	Hiemstra, PS
dc.contributor.author	van Hemert, MJ
dc.date.accessioned	2023-09-28T01:20:13Z
dc.date.available	2023-03-03
dc.date.available	2023-09-28T01:20:13Z
dc.date.issued	2023-03-25
dc.identifier.citation	J Innate Immun, 2023, 15, (1), pp. 562-580
dc.identifier.issn	1662-811X
dc.identifier.issn	1662-8128
dc.identifier.uri	http://hdl.handle.net/10453/172357
dc.description.abstract	The consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can range from asymptomatic to fatal disease. Variations in epithelial susceptibility to SARS-CoV-2 infection depend on the anatomical location from the proximal to distal respiratory tract. However, the cellular biology underlying these variations is not completely understood. Thus, air-liquid interface (ALI) cultures of well-differentiated primary human tracheal and bronchial epithelial cells were employed to study the impact of epithelial cellular composition and differentiation on SARS-CoV-2 infection by transcriptional (RNA sequencing) and immunofluorescent analyses. Changes of cellular composition were investigated by varying time of differentiation or by using specific compounds. We found that SARS-CoV-2 primarily infected ciliated cells but also goblet cells and transient secretory cells. Viral replication was impacted by differences in cellular composition, which depended on culturing time and anatomical origin. A higher percentage of ciliated cells correlated with a higher viral load. However, DAPT-treatment, which increased number of ciliated cells and reduced goblet cells, decreased viral load, indicating the contribution of goblet cells to infection. Cell-entry factors, especially cathepsin L and transmembrane protease serine 2, were also affected by differentiation time. In conclusion, our study demonstrates that viral replication is affected by changes in cellular composition, especially in cells related to the mucociliary system. This could explain in part the variable susceptibility to SARS-CoV-2 infection between individuals and between anatomical locations in the respiratory tract.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Karger Publishers
dc.relation.ispartof	J Innate Immun
dc.relation.isbasedon	10.1159/000530374
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	11 Medical and Health Sciences
dc.subject.classification	3202 Clinical sciences
dc.subject.classification	3204 Immunology
dc.subject.classification	3207 Medical microbiology
dc.title	Impact of changes in human airway epithelial cellular composition and differentiation on SARS-CoV-2 infection biology.
dc.type	Journal Article
utslib.citation.volume	15
utslib.location.activity	Switzerland
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
pubs.organisational-group	/University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	open_access	*
dc.date.updated	2023-09-28T01:20:07Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	15
utslib.citation.issue	1

Abstract:

The consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can range from asymptomatic to fatal disease. Variations in epithelial susceptibility to SARS-CoV-2 infection depend on the anatomical location from the proximal to distal respiratory tract. However, the cellular biology underlying these variations is not completely understood. Thus, air-liquid interface (ALI) cultures of well-differentiated primary human tracheal and bronchial epithelial cells were employed to study the impact of epithelial cellular composition and differentiation on SARS-CoV-2 infection by transcriptional (RNA sequencing) and immunofluorescent analyses. Changes of cellular composition were investigated by varying time of differentiation or by using specific compounds. We found that SARS-CoV-2 primarily infected ciliated cells but also goblet cells and transient secretory cells. Viral replication was impacted by differences in cellular composition, which depended on culturing time and anatomical origin. A higher percentage of ciliated cells correlated with a higher viral load. However, DAPT-treatment, which increased number of ciliated cells and reduced goblet cells, decreased viral load, indicating the contribution of goblet cells to infection. Cell-entry factors, especially cathepsin L and transmembrane protease serine 2, were also affected by differentiation time. In conclusion, our study demonstrates that viral replication is affected by changes in cellular composition, especially in cells related to the mucociliary system. This could explain in part the variable susceptibility to SARS-CoV-2 infection between individuals and between anatomical locations in the respiratory tract.

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http://hdl.handle.net/10453/172357