An Organoid-derived Bronchioalveolar Model for SARS-CoV-2 Infection of Human Alveolar-type II-like Cells

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 -