Abstract
AbstractBackground: Respiratory syncytial virus (RSV) is a major cause of infant morbidity and hospitalisation, particularly in winter. It is the leading cause of bronchiolitis in infants, marked by mucus overproduction and airway inflammation. Infants with cystic fibrosis (CF) may be more susceptible, but the consequences of RSV infection in CF compared with healthy airway epithelium remains unclear.
Aim: To develop a well-differentiated primary nasal epithelial cell (WD-PNEC) model derived from newly diagnosed CF infants under 12 weeks old and compare RSV infection outcomes—cell tropism, viral growth kinetics, cytopathogenesis, and innate immune responses—with those in healthy controls.
Methods: Primary nasal cells from CF and healthy infants were cultured into WD-PNECs. Once fully differentiated, cultures were mock or RSV- infected with RSV BT2a (MOI 3). Apical and basal media were collected at 24, 48, 72, and 96 hpi for viral titration and investigation immune responses. TEER measured epithelial integrity, and immunofluorescence assessed cell composition and RSV tropism. RT-qPCR, BioPlex, and ELISA evaluated innate immune responses; cDNA was prepared for future NGS.
Results: WD-PNECs were successfully established from both groups. CF cultures showed thicker mucus. RSV infected both CF and healthy WD-PNECs with no significant difference in viral replication. IL-29 secretion was robust in both groups. Minor differences were observed in cytokine profiles and DUOX2 gene expression. The results of NGS data are pending analysis and will provide a valuable contribution for future work.
Conclusion: The results suggest RSV infection in CF and healthy infant nasal epithelium produced broadly similar outcomes, suggesting shared innate responses during early infancy.
Thesis is embargoed until 31 July 2026.
| Date of Award | Jul 2025 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Sponsors | Royal Belfast Hospital for Sick Children |
| Supervisor | Ultan Power (Supervisor) & Mike Shields (Supervisor) |
Keywords
- Cystic fibrosis
- RSV
- respiratory syncytial virus
- respiratory epithelium
- innate immune response infant