An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells.
Mart M Lamers, Jelte van der Vaart, Kèvin Knoops, Samra Riesebosch, Tim I Breugem, Anna Z Mykytyn, Joep Beumer, Debby Schipper, Karel Bezstarosti, Charlotte D Koopman, Nathalie Groen, Raimond B G Ravelli, Hans Q Duimel, Jeroen A A Demmers, Georges M G M Verjans, Marion P G Koopmans, Mauro J Muraro, Peter J Peters, Hans Clevers, Bart L Haagmans
Author Information
Mart M Lamers: Viroscience Department, Erasmus University Medical Center, Rotterdam, The Netherlands. ORCID
Jelte van der Vaart: Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, The Netherlands. ORCID
Kèvin Knoops: The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, The Netherlands.
Samra Riesebosch: Viroscience Department, Erasmus University Medical Center, Rotterdam, The Netherlands.
Tim I Breugem: Viroscience Department, Erasmus University Medical Center, Rotterdam, The Netherlands.
Anna Z Mykytyn: Viroscience Department, Erasmus University Medical Center, Rotterdam, The Netherlands.
Joep Beumer: Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, The Netherlands. ORCID
Debby Schipper: Viroscience Department, Erasmus University Medical Center, Rotterdam, The Netherlands.
Karel Bezstarosti: Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands.
Charlotte D Koopman: Single Cell Discoveries, Utrecht, The Netherlands.
Nathalie Groen: Single Cell Discoveries, Utrecht, The Netherlands.
Raimond B G Ravelli: The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, The Netherlands.
Hans Q Duimel: The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, The Netherlands.
Jeroen A A Demmers: Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands.
Georges M G M Verjans: Viroscience Department, Erasmus University Medical Center, Rotterdam, The Netherlands. ORCID
Marion P G Koopmans: Viroscience Department, Erasmus University Medical Center, Rotterdam, The Netherlands.
Mauro J Muraro: Single Cell Discoveries, Utrecht, The Netherlands.
Peter J Peters: The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, The Netherlands.
Hans Clevers: Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, The Netherlands. ORCID
Bart L Haagmans: Viroscience Department, Erasmus University Medical Center, Rotterdam, The Netherlands. ORCID
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.
