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 - Publisher Copyright:
© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license
PY - 2021/3/1
Y1 - 2021/3/1
N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which may result in acute respiratory distress syndrome (ARDS), multiorgan 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 and 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) causes coronavirus disease 2019 (COVID-19), which may result in acute respiratory distress syndrome (ARDS), multiorgan 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 and 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.
KW - COVID-19
KW - SARS-CoV-2
KW - airway organoids
KW - bronchioalveolar-like
KW - pneumocytes
UR - https://www.scopus.com/pages/publications/85099097921
U2 - 10.15252/embj.2020105912
DO - 10.15252/embj.2020105912
M3 - Article
C2 - 33283287
AN - SCOPUS:85099097921
SN - 0261-4189
VL - 40
JO - EMBO Journal
JF - EMBO Journal
IS - 5
M1 - e105912
ER -