Early life innate immune responses to RSV in cystic fibrosis airway epithelium: Poster A244 P 247

Respiratory syncytial virus (RSV) infection is the major cause of severe lower respiratory tract disease in young
infants. Evidence suggests that cystic fibrosis (CF) is associated with significant morbidity following RSV infection.
We and others previously demonstrated that airway epithelium is the primary target of RSV infection. However,
little is known about the impact of RSV infection on CF airway epithelium. To address this, we established and
characterised well-differentiated primary nasal epithelial cell cultures (WD-PNECs) from recently diagnosed CF
infants to study RSV cytopathogenesis in CF airway epithelium. CF WD-PNECs were successfully generated from 11
infants and characterised by light and fluorescent microscopy. CF WD-PNECs secreted thick dry apical mucous,
consistent with in vivo observations. Extensive cilia coverage was also evident, although cilia beat frequencies
appeared lower than those evident in WD-PNECs from healthy neonates. Quantification of goblet and ciliated cells
in the CF WD-PNEC cultures were similar to those of healthy cultures. Viral growth kinetics were similar for CF
WD-PNECs and healthy WD- PNECs, with peak virus titres evident at 72-96 hpi. CXCL8/IL-8 and CXCL10/IP-10
secretions were upregulated following RSV infection of CF WD-PNECs, while IL-6 secretions did not change.
Interestingly, our data suggested that duoxa2 and duox2 expression post-infection were reduced in WD-PNECs
from CF compared to healthy infants. Our data suggest that this model provides an exciting opportunity to
elucidate the cytopathogenic, inflammatory and molecular consequences of RSV infection of airway epithelium
derived from very young CF infant