1. An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells
- Author
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Peter J. Peters, Bart L. Haagmans, Nathalie Groen, Jelte van der Vaart, Debby Schipper, Jeroen Demmers, Kèvin Knoops, Tim I Breugem, Hans Duimel, Hans Clevers, Marion Koopmans, Mauro J. Muraro, Samra Riesebosch, Joep Beumer, Karel Bezstarosti, Georges M. G. M. Verjans, Anna Z Mykytyn, Mart M. Lamers, Raimond B. G. Ravelli, Charlotte D. Koopman, Hubrecht Institute for Developmental Biology and Stem Cell Research, Institute of Nanoscopy (IoN), RS: M4I - Nanoscopy, Virology, and Biochemistry
- Subjects
PNEUMONIA ,ARDS ,viruses ,Respiratory System ,Cell ,coronavirus ,ACE2 ,Virus Replication ,SARS‐CoV‐2 ,Interferon Lambda ,stem-cells ,HOSPITALIZED-PATIENTS ,0302 clinical medicine ,STAT1 ,Interferon ,Chlorocebus aethiops ,membrane ,0303 health sciences ,General Neuroscience ,Articles ,differentiation ,progenitor cells ,Microbiology, Virology & Host Pathogen Interaction ,3. Good health ,Organoids ,bronchioalveolar-like ,medicine.anatomical_structure ,Interferon Type I ,medicine.drug ,EXPRESSION ,Alveolar Epithelium ,Methods & Resources ,Biology ,Models, Biological ,Article ,General Biochemistry, Genetics and Molecular Biology ,Virus ,lung ,Alveolar cells ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,COVID‐19 ,medicine ,Organoid ,Animals ,Humans ,Vero Cells ,Molecular Biology ,030304 developmental biology ,General Immunology and Microbiology ,SARS-CoV-2 ,COVID-19 ,pneumocytes ,medicine.disease ,Virology ,airway organoids ,Gene Expression Regulation ,Viral replication ,Alveolar Epithelial Cells ,Interferons ,bronchioalveolar‐like ,030217 neurology & neurosurgery - 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, 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., A human airway in vitro culture permissive to COVID‐19 demonstrates a drug‐sensitive IFN response.
- Published
- 2021