An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells
Lamers, Mart M; van der Vaart, Jelte; Knoops, Kèvin; Riesebosch, Samra; Breugem, Tim I; Mykytyn, Anna Z; Beumer, Joep; Schipper, Debby; Bezstarosti, Karel; Koopman, Charlotte D; Groen, Nathalie; Ravelli, Raimond B G; Duimel, Hans Q; Demmers, Jeroen A A; Verjans, Georges M G M; Koopmans, Marion P G; Muraro, Mauro J; Peters, Peter J; Clevers, Hans; Haagmans, Bart L
(2021) EMBO Journal, volume 40, issue 5
(Article)
Abstract
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,
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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.
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Keywords: airway organoids, bronchioalveolar-like, COVID-19, pneumocytes, SARS-CoV-2, General Biochemistry,Genetics and Molecular Biology, General Immunology and Microbiology, Molecular Biology, General Neuroscience, Journal Article
ISSN: 0261-4189
Publisher: Nature Publishing Group
Note: Funding Information: We thank A de Graaff and Hubrecht Imaging Centre (HIC) for microscopy assistance and Single Cell Discoveries for single‐cell sequencing and mRNA library preparation, and the Utrecht Sequencing Facility (subsidized by the University Medical Center Utrecht, Hubrecht Institute, Utrecht University and NWO project 184.034.019). KK, PJP, and RBGR received funding from the Dutch Technology Foundation STW under project name UPON, number 14207. We acknowledge the Maastricht M4I Microscopy CORE Lab for their scientific and technological support. This work was supported by NWO Grant 022.005.032. We thank Evelien Eenjes and Robbert Rottier for providing human adult lung material. Publisher Copyright: © 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license
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