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

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), may result in acute respiratory distress syndrome (ARDS), multi-organ 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-, 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.

Original languageEnglish
Pages (from-to)e105912
JournalEMBO Journal
DOIs
Publication statusE-pub ahead of print - 06 Dec 2020

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