tetano
Editor, Senior Moderator
J Infect Dis
. 2025 Mar 11:jiaf125.
doi: 10.1093/infdis/jiaf125. Online ahead of print. SARS-CoV-2 infection of human lung ALI cultures reveals basal cells as relevant targets
Morris Baumgardt[SUP] 1 [/SUP], Benedikt Obermayer[SUP] 2 [/SUP], Anita Balázs[SUP] 3 4 [/SUP], Anna Löwa[SUP] 1 [/SUP], Emanuel Wyler[SUP] 5 [/SUP], Luiz Gustavo Teixeira Alves[SUP] 5 [/SUP], Katharina Hellwig[SUP] 1 [/SUP], Dieter Beule[SUP] 2 [/SUP], Markus Landthaler[SUP] 5 6 [/SUP], Marcel A Müller[SUP] 7 [/SUP], Christian Drosten[SUP] 7 [/SUP], Marcus A Mall[SUP] 3 4 8 [/SUP], Stefan Hippenstiel[SUP] 1 [/SUP], Katja Hönzke[SUP] 1 9 [/SUP], Andreas C Hocke[SUP] 1 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily targets ciliated cells during the initial infection of the upper respiratory tract. Since uncertainties persist regarding other involved epithelial cell types, we here utilized viral replication analysis, single-cell RNA sequencing, and spectral microscopy on infected air-liquid interface cultures of human primary nasal and bronchial epithelial cells to discern cell type proportions in relation to SARS-CoV-2 tropism and immune activation. We revealed that, next to ciliated and secretory cells, SARS-CoV-2 (wild type and lineage B1.1.7 [Alpha variant]) strongly infects basal cells, significantly contributing to the epithelial immune response in a donor-specific manner. Moreover, local Camostat mesylate treatment was effective on both the basal and apical cell compartment, resulting in a notable reduction in viral load and reduced immune activation. Collectively, our data emphasize the critical role of basal cells in facilitating SARS-CoV-2 dissemination within the upper respiratory tract and their substantial contribution to the epithelial immune response. Furthermore, our results highlight the potential of local application of Camostat mesylate as an effective strategy for inhibiting SARS-CoV-2 infection and mitigating associated immune activation early on.
Keywords: Camostat mesylate; SARS-CoV-2; URT; basal cells; epithelial immune response; viral tropism.
. 2025 Mar 11:jiaf125.
doi: 10.1093/infdis/jiaf125. Online ahead of print. SARS-CoV-2 infection of human lung ALI cultures reveals basal cells as relevant targets
Morris Baumgardt[SUP] 1 [/SUP], Benedikt Obermayer[SUP] 2 [/SUP], Anita Balázs[SUP] 3 4 [/SUP], Anna Löwa[SUP] 1 [/SUP], Emanuel Wyler[SUP] 5 [/SUP], Luiz Gustavo Teixeira Alves[SUP] 5 [/SUP], Katharina Hellwig[SUP] 1 [/SUP], Dieter Beule[SUP] 2 [/SUP], Markus Landthaler[SUP] 5 6 [/SUP], Marcel A Müller[SUP] 7 [/SUP], Christian Drosten[SUP] 7 [/SUP], Marcus A Mall[SUP] 3 4 8 [/SUP], Stefan Hippenstiel[SUP] 1 [/SUP], Katja Hönzke[SUP] 1 9 [/SUP], Andreas C Hocke[SUP] 1 [/SUP]
Affiliations
- PMID: 40065723
- DOI: 10.1093/infdis/jiaf125
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily targets ciliated cells during the initial infection of the upper respiratory tract. Since uncertainties persist regarding other involved epithelial cell types, we here utilized viral replication analysis, single-cell RNA sequencing, and spectral microscopy on infected air-liquid interface cultures of human primary nasal and bronchial epithelial cells to discern cell type proportions in relation to SARS-CoV-2 tropism and immune activation. We revealed that, next to ciliated and secretory cells, SARS-CoV-2 (wild type and lineage B1.1.7 [Alpha variant]) strongly infects basal cells, significantly contributing to the epithelial immune response in a donor-specific manner. Moreover, local Camostat mesylate treatment was effective on both the basal and apical cell compartment, resulting in a notable reduction in viral load and reduced immune activation. Collectively, our data emphasize the critical role of basal cells in facilitating SARS-CoV-2 dissemination within the upper respiratory tract and their substantial contribution to the epithelial immune response. Furthermore, our results highlight the potential of local application of Camostat mesylate as an effective strategy for inhibiting SARS-CoV-2 infection and mitigating associated immune activation early on.
Keywords: Camostat mesylate; SARS-CoV-2; URT; basal cells; epithelial immune response; viral tropism.