tetano
Editor, Senior Moderator
EMBO J
. 2020 Dec 6;e105912.
doi: 10.15252/embj.2020105912. Online ahead of print.
An Organoid-derived Bronchioalveolar Model for SARS-CoV-2 Infection of Human Alveolar-type II-like Cells
Mart M Lamers[SUP] 1 [/SUP], Jelte van der Vaart[SUP] 2 [/SUP], K?vin Knoops[SUP] 3 [/SUP], Samra Riesebosch[SUP] 1 [/SUP], Tim I Breugem[SUP] 1 [/SUP], Anna Z Mykytyn[SUP] 1 [/SUP], Joep Beumer[SUP] 2 [/SUP], Debby Schipper[SUP] 1 [/SUP], Karel Bezstarosti[SUP] 4 [/SUP], Charlotte D Koopman[SUP] 5 [/SUP], Nathalie Groen[SUP] 5 [/SUP], Raimond B G Ravelli[SUP] 3 [/SUP], Hans Q Duimel[SUP] 3 [/SUP], Jeroen A A Demmers[SUP] 4 [/SUP], Georges M G M Verjans[SUP] 1 [/SUP], Marion P G Koopmans[SUP] 1 [/SUP], Mauro J Muraro[SUP] 5 [/SUP], Peter J Peters[SUP] 3 [/SUP], Hans Clevers[SUP] 2 [/SUP], Bart L Haagmans[SUP] 1 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), may result in acute respiratory distress syndrome (ARDS), multi-organ failure and death. The alveolar epithelium is a major target of the virus, but representative models to study virus host interactions in more detail are currently lacking. Here, we describe a human 2D air-liquid interface culture system which was characterized by confocal-, electron-microscopy and single cell mRNA expression analysis. In this model, alveolar cells, but also basal cells and rare neuroendocrine cells, are grown from 3D self-renewing fetal lung bud tip organoids. These cultures were readily infected by SARS-CoV-2 with mainly surfactant protein C-positive alveolar type II-like cells being targeted. Consequently, significant viral titers were detected and mRNA expression analysis revealed induction of type I/III interferon response program. Treatment of these cultures with a low dose of interferon lambda 1 reduced viral replication. Hence, these cultures represent an experimental model for SARS-CoV-2 infection and can be applied for drug screens.
Keywords: COVID-19; SARS-CoV-2; airway organoids; bronchioalveolar-like; pneumocytes.
. 2020 Dec 6;e105912.
doi: 10.15252/embj.2020105912. Online ahead of print.
An Organoid-derived Bronchioalveolar Model for SARS-CoV-2 Infection of Human Alveolar-type II-like Cells
Mart M Lamers[SUP] 1 [/SUP], Jelte van der Vaart[SUP] 2 [/SUP], K?vin Knoops[SUP] 3 [/SUP], Samra Riesebosch[SUP] 1 [/SUP], Tim I Breugem[SUP] 1 [/SUP], Anna Z Mykytyn[SUP] 1 [/SUP], Joep Beumer[SUP] 2 [/SUP], Debby Schipper[SUP] 1 [/SUP], Karel Bezstarosti[SUP] 4 [/SUP], Charlotte D Koopman[SUP] 5 [/SUP], Nathalie Groen[SUP] 5 [/SUP], Raimond B G Ravelli[SUP] 3 [/SUP], Hans Q Duimel[SUP] 3 [/SUP], Jeroen A A Demmers[SUP] 4 [/SUP], Georges M G M Verjans[SUP] 1 [/SUP], Marion P G Koopmans[SUP] 1 [/SUP], Mauro J Muraro[SUP] 5 [/SUP], Peter J Peters[SUP] 3 [/SUP], Hans Clevers[SUP] 2 [/SUP], Bart L Haagmans[SUP] 1 [/SUP]
Affiliations
- PMID: 33283287
- DOI: 10.15252/embj.2020105912
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), may result in acute respiratory distress syndrome (ARDS), multi-organ failure and death. The alveolar epithelium is a major target of the virus, but representative models to study virus host interactions in more detail are currently lacking. Here, we describe a human 2D air-liquid interface culture system which was characterized by confocal-, electron-microscopy and single cell mRNA expression analysis. In this model, alveolar cells, but also basal cells and rare neuroendocrine cells, are grown from 3D self-renewing fetal lung bud tip organoids. These cultures were readily infected by SARS-CoV-2 with mainly surfactant protein C-positive alveolar type II-like cells being targeted. Consequently, significant viral titers were detected and mRNA expression analysis revealed induction of type I/III interferon response program. Treatment of these cultures with a low dose of interferon lambda 1 reduced viral replication. Hence, these cultures represent an experimental model for SARS-CoV-2 infection and can be applied for drug screens.
Keywords: COVID-19; SARS-CoV-2; airway organoids; bronchioalveolar-like; pneumocytes.