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

EMBO J. 2021 Mar 1;40(5):e105912. doi: 10.15252/embj.2020105912. Epub 2021 Jan 11.

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.

Keywords: COVID-19; SARS-CoV-2; airway organoids; bronchioalveolar-like; pneumocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Epithelial Cells / metabolism*
  • Alveolar Epithelial Cells / pathology
  • Alveolar Epithelial Cells / virology
  • Animals
  • COVID-19 / metabolism*
  • COVID-19 / virology
  • Chlorocebus aethiops
  • Gene Expression Regulation
  • Humans
  • Interferon Type I / biosynthesis
  • Interferons / biosynthesis
  • Models, Biological*
  • Organoids / metabolism*
  • Organoids / pathology
  • Organoids / virology
  • SARS-CoV-2 / physiology*
  • Vero Cells
  • Virus Replication*

Substances

  • Interferon Type I
  • interferon type III
  • Interferons

Associated data

  • GEO/GSE153218
  • GEO/GSE161934