An organoid‐derived bronchioalveolar model for SARS‐CoV‐2 infection of human alveolar type II‐like cells
Open accessAbstract
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.
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SARS-CoV-2 infection in organoids produced weak interferon responses, and infected bioengineered lung models shared interferon signatures with native human lungs.
“Organoids demonstrated the induction of inefficient interferon responses in SARS-CoV-2 infections84,85, revealing similar interferon signatures between SARS-CoV-2-infected bioengineered lung models and native human lungs”
From Human disease models in drug development (2023) · cites this paper as [85]
The Host responses section reports that SARS-CoV-2 infection induced a broad type I/III interferon-stimulated gene signature in the organoid-derived cultures. It does not characterize that response as weak or inefficient. The section compares the induction with a report on human bronchial epithelial cells, not with interferon signatures in native human lungs; no page number is available in our copy. (LLM, conf=0.84)
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References 70 · Cited by 227
- Authors
- Lamers, M. M., van der Vaart, J., Knoops, K., Riesebosch, S., Breugem, T. I., Mykytyn, A. Z., Beumer, J., Schipper, D., Bezstarosti, K., Koopman, C. D., Groen, N., Ravelli, R. B. G., Duimel, H. Q., Demmers, J. A. A., Verjans, G. M. G. M., Koopmans, M. P. G., Muraro, M. J., Peters, P. J., Clevers, H., & Haagmans, B. L.
- Affiliations
- Erasmus MC (NL)
- Maastricht University (NL)
- Royal Netherlands Academy of Arts and Sciences (NL)
- Single Cell Discoveries (Netherlands) (NL)
- Corresponding author
- Clevers, Hans
- Haagmans, Bart L
- ORCID
- Venue
- The EMBO Journal
- Published
- 2021-01-11
- Volume
- 40
- Issue
- 5
- Pages
- e105912-e105912
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC7883112
- OpenAlex
- W3111167477
- Cited by
- 227
- References
- 70
- Citations by year
- 2026: 21 · 2025: 34 · 2024: 22 · 2023: 44 · 2022: 61 · 2021: 45
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by-nc-nd)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, cc-by-nc-nd)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, cc-by-nc-nd)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- NWO | Stichting voor de Technische Wetenschappen (14207)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (022.005.032, 184.034.019)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- SARS-CoV-2, COVID-19 pandemic, lung organoids, air-liquid interface culture, alveolar type II cells, surfactant protein C, alveolar epithelium, interferon lambda, interferon response, viral replication, basal cells, neuroendocrine cells, drug screening model
- MeSH terms
- COVID-19, SARS-CoV-2, Interferon Lambda, Animals, Chlorocebus aethiops, Gene Expression Regulation, Humans, Interferon Type I, Interferons, Models, Biological, Organoids, Vero Cells, Virus Replication, Alveolar Epithelial Cells
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