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An organoid‐derived bronchioalveolar model for SARS‐CoV‐2 infection of human alveolar type II‐like cells
Author(s) -
Lamers Mart M,
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
Publication year - 2021
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020105912
Subject(s) - organoid , biology , covid-19 , type (biology) , virology , computational biology , microbiology and biotechnology , pathology , ecology , medicine , disease , outbreak , infectious disease (medical specialty)
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.