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

M.M. Lamers, J. van der Vaart, K. Knoops, S. Riesebosch, T.I. Breugem, A.Z. Mykytyn, J. Beumer, D. Schipper, K. Bezstarosti, C.D. Koopman, N. Groen, R.B.G. Ravelli, H.Q. Duimel, J.A.A. Demmers, G.M.G.M. Verjans, M.P.G. Koopmans, M.J. Muraro, P.J. Peters, H. Clevers*, B.L. Haagmans*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

71 Citations (Web of Science)

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.
Original languageEnglish
Article number105912
Number of pages19
JournalThe Embo Journal
Volume40
Issue number5
DOIs
Publication statusPublished - 1 Mar 2021

Keywords

  • ACE2
  • CORONAVIRUS
  • COVID-19
  • DIFFERENTIATION
  • EXPRESSION
  • LUNG
  • MEMBRANE
  • PNEUMONIA
  • PROGENITOR CELLS
  • SARS-CoV-2
  • STAT1
  • STEM-CELLS
  • ace2
  • airway organoids
  • bronchioalveolar-like
  • coronavirus
  • covid-19
  • differentiation
  • expression
  • lung
  • membrane
  • pneumocytes
  • pneumonia
  • progenitor cells
  • sars-cov-2
  • stem-cells
  • HOSPITALIZED-PATIENTS

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