Background: Human 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.
Methods: Between 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.
Findings: Virus 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.
Interpretation: Human 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.
Funding: US National Institute of Allergy and Infectious Diseases, Research Grants Council of the Hong Kong Special Administrative Region.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/S2213-2600(18)30236-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Epithelial-to-mesenchymal transition and live cell extrusion contribute to measles virus release from human airway epithelia.
J Virol
January 2025
Microbiology and Immunology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
Measles virus (MeV) is a highly contagious respiratory virus transmitted via aerosols. To understand how MeV exits the airways of an infected host, we use unpassaged primary cultures of human airway epithelial cells (HAE). MeV typically remains cell-associated in HAE and forms foci of infection, termed infectious centers, by directly spreading cell-to-cell.
View Article and Find Full Text PDFCCL4 Affects Eosinophil Survival via the Shedding of the MUC1 N-Terminal Domain in Airway Inflammation.
Cells
December 2024
Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan.
Eosinophilic chronic rhinosinusitis (ECRS), a CRS with nasal polyps (CRSwNP), is characterized by eosinophilic infiltration with type 2 inflammation and is highly associated with bronchial asthma. Intractable ECRS with poorly controlled asthma is recognized as a difficult-to-treat eosinophilic airway inflammation. Although eosinophils are activated and coincubation with airway epithelial cells prolongs their survival, the interaction mechanism between eosinophils and epithelial cells is unclear.
View Article and Find Full Text PDFEpigenetic Inhibitors Differentially Impact TGF-β1 Signaling Cascades in COPD Airway Smooth Muscle Cells.
Cells
December 2024
School of Life Science, University of Technology Sydney, Ultimo, NSW 2007, Australia.
Chronic obstructive pulmonary disease (COPD) is characterized by progressive and incurable airflow obstruction and chronic inflammation. Both TGF-β1 and CXCL8 have been well described as fundamental to COPD progression. DNA methylation and histone acetylation, which are well-understood epigenetic mechanisms regulating gene expression, are associated with COPD progression.
View Article and Find Full Text PDFAssociation Between Chronic Obstructive Pulmonary Disease and Rheumatoid Arthritis: Findings of the Observational and Mendelian Randomization Study.
Int J Rheum Dis
January 2025
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Army Medical University, Chongqing, China.
Background: Airway inflammation is considered one of the pathogenic factors in rheumatoid arthritis (RA), but the role of chronic obstructive pulmonary disease (COPD) in the development of RA remains unclear. We used cross-sectional studies and Mendelian randomization (MR) analysis to explore the link between COPD and RA.
Methods: In National Health and Nutrition Examination Survey (NHANES) 2013-2018, the association between COPD and RA was investigated using weighted logistic regression models.
Novel Cystic Fibrosis Ferret Model Enables Visualization of CFTR Expression Cells and Genetic CFTR Reactivation.
Hum Gene Ther
January 2025
Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Cystic fibrosis (CF) is caused by mutations in the (). While gene therapy holds promise as a cure, the cell-type-specific heterogeneity of expression in the lung presents significant challenges. Current CF ferret models closely replicate the human disease phenotype but have limitations in studying functional complementation through cell-type-specific CFTR restoration.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!