TY - JOUR
T1 - An Organoid-derived Bronchioalveolar Model for SARS-CoV-2 Infection of Human Alveolar-type II-like Cells
AU - Lamers, Mart M
AU - van der Vaart, Jelte
AU - Knoops, Kèvin
AU - Riesebosch, Samra
AU - Breugem, Tim I
AU - Mykytyn, Anna Z
AU - Beumer, Joep
AU - Schipper, Debby
AU - Bezstarosti, Karel
AU - Koopman, Charlotte D
AU - Groen, Nathalie
AU - Ravelli, Raimond B G
AU - Duimel, Hans Q
AU - Demmers, Jeroen A A
AU - Verjans, Georges M G M
AU - Koopmans, Marion P G
AU - Muraro, Mauro J
AU - Peters, Peter J
AU - Clevers, Hans
AU - Haagmans, Bart L
N1 - This article is protected by copyright. All rights reserved.
PY - 2020/12/6
Y1 - 2020/12/6
N2 - 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.
AB - 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.
U2 - 10.15252/embj.2020105912
DO - 10.15252/embj.2020105912
M3 - Article
C2 - 33283287
SN - 0261-4189
SP - e105912
JO - EMBO Journal
JF - EMBO Journal
ER -