An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells

Autor: 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
Přispěvatelé: Hubrecht Institute for Developmental Biology and Stem Cell Research, Institute of Nanoscopy (IoN), RS: M4I - Nanoscopy, Virology, Biochemistry
Jazyk: angličtina
Rok vydání: 2021
Předmět:
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
Zdroj: EMBO Journal. Nature Publishing Group
The EMBO Journal
The Embo Journal, 40(5):105912. Wiley
EMBO Journal, 40(5):e105912. Wiley-Blackwell
ISSN: 1460-2075
0261-4189
Popis: 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.
Databáze: OpenAIRE
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