ArticleThe Lancet. Respiratory medicine2018
Tropism, replication competence, and innate immune responses of influenza virus: an analysis of human airway organoids and ex-vivo bronchus cultures.
Article in The Lancet. Respiratory medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 3 of them syntheses that pooled it.
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Who cites it
95 citing papers in PubMed, 3 syntheses or guidelines pooled it, 144 citations in OpenAlex.
- Lung Organoids: Systematic Review of Recent Advancements and its Future Perspectives.Tissue engineering and regenerative medicine · 2024Pooled it
- Recent Advances in Graphene Oxide-Based on Organoid Culture as Disease Model and Cell Behavior - A Systematic Literature Review.International journal of nanomedicine · 2024Pooled it
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- Tropism, replication competence, and cellular responses of HAdV-14p1 in human airway organoids.iScience · 2026Article
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- Post-Translational Modifications in Respiratory Virus Infection: Recent Insights into the Development of In Vitro Models.International journal of molecular sciences · 2025Review
- Emerging highly pathogenic H5N1 influenza triggers fibrotic remodeling in human airway organoids.Emerging microbes & infections · 2025Article
- Old World alphaviruses use distinct mechanisms to infect brain microvascular endothelial cells for neuroinvasion.Cell reports · 2025Article
- MERS-CoV and SARS-CoV-2 infection in diverse human lung organoid-derived cultures.Journal of virology · 2025Article
- Organoids: physiologically relevantJournal of virology · 2025Review
- The long reach of influenza and other respiratory viruses: from acute epithelial injury to post-viral lung disease.Clinical microbiology reviews · 2025Review
- Applications and research trends in organoid based infectious disease models.Scientific reports · 2025Review
- The Originally Established PBE Cell Line as a Reliable In Vitro Model for Investigating SIV Infection and Immunity.International journal of molecular sciences · 2025Article
- Cryopreservation of human lung tissue for 3D ex vivo analysis.Respiratory research · 2025Review
- Dynamic Interaction Between SARS-CoV-2 and Influenza A Virus Infection in Human Respiratory Tissues and Cells.Microorganisms · 2025Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundHuman airway organoids are three-dimensional cultures derived from stem cells, which self-organise in ex-vivo conditions to form so-called mini-airways. The cellular morphology of these cultures is physiologically similar to the human airway, with cilia, goblet cells, and club cells facing the inner lumen and basal cells situated at the outer layer. The aim of this study was to compare replication competence, tissue tropism, and host responses elicited by human and avian strains of influenza A virus in ex-vivo human bronchus and human airway organoids.
methodsBetween Sept 29, 2016, and Jan 4, 2017, we obtained ex-vivo cultures of the human bronchus and cultured human airway organoids from lung stem cells obtained from human lung tissues removed as part of the routine clinical care of patients undergoing surgical resection at the Department of Cardiothoracic Surgery, University of Hong Kong, Queen Mary Hospital, Hong Kong. We compared viral replication competence, tissue tropism, and cytokine and chemokine induction of avian influenza A viruses isolated from humans (Sh2/H7N9, H5N1/483, H5N6/39715), and human H1N1pdm/415742 in airway organoids and ex-vivo bronchus explant cultures.
findingsVirus tropism and replication kinetics of human and avian influenza A viruses in human airway organoids mimicked those found in ex-vivo cultures of human bronchus explants. In both airway organoids and bronchus explants, influenza A H1N1 subtype (H1N1) and avian influenza A H7N9 viruses replicated to significantly higher titres than did the highly pathogenic avian influenza (HPAI) H5N1, whereas HPAI H5N6 replication was moderate. H1N1, H7N9, and H5N6 viruses infected ciliated cells and goblet cells, but not basal cells in both airway organoids and bronchus explants. The expression of cytokines, interleukin 6, and interferon β, and the chemokine regulated-on-activation, normal T-cell expressed and secreted, was significantly higher in human airway organoids infected with HPAI H5N1 virus than H1N1pdm/415742, Sh2/H7N9, and H5N6/39715 viruses, and the expression of monocyte chemoattractant protein-1 was significantly higher in human organoids infected with HPAI H5N1 virus than H1N1pdm/415742 and Sh2/H7N9 viruses.
interpretationHuman airway organoid cultures provided results that were comparable to those observed in human ex-vivo bronchus cultures, and thus provide an alternative physiologically relevant experimental model for investigating virus tropism and replication competence that could be used to assess the pandemic threat of animal influenza viruses.
fundingUS National Institute of Allergy and Infectious Diseases, Research Grants Council of the Hong Kong Special Administrative Region.
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