Airway epithelial cells from asthmatic adults support elevated human metapneumovirus infection due to impaired apoptosis
Engin Baturcam (Herston, Australia), Engin Baturcam, Tiong Han Yeo, Johanna Schagen, Natale Snape, Emma Thomas, Janine Di-Masi, Sally Galbraith, Simon Phipps, Emmanuelle Fantino, Peter Sly, Kirsten Spann
Source: International Congress 2015 – Advances from translational research in respiratory infections
Disease area: Airway diseases
Abstract The susceptibility to viral infection of the airway epithelium is greater in subjects with asthma compared to those without asthma. Using primary paediatric nasal epithelial cells (NECs) we have previously demonstrated that this susceptibility is independent of the host's ability to produce interferons (IFN). Here we used NECs from moderate atopic asthmatic (n = 10) and non-asthmatic (n = 10) adults in submerged monolayer cultures to study antiviral cell death responses. Cells were infected with respiratory syncytial virus (RSV A2) and human metapneumovirus (hMPV CAN-97/83) and the response characterised within 24h p.i. at a high multiplicity of infection (MOI 3). NECs from asthmatics were IFN competent and supported elevated hMPV, but not RSV, infection compared to non-asthmatic controls (p<0.05). Annexin-V staining revealed reduced apoptosis in response to hMPV, but not RSV, in NECs from asthmatics 24h p.i. (p<0.01), which correlated to reduced activation of caspase-9 and -3/7 (p<0.01 and p<0.0001 respectively). However, hMPV induced Endoplasmic Reticulum specific pro-apoptotic factors (CHOP, PUMA and NOXA) similarly in NECs from asthmatics and non-asthmatics. This suggests that asthmatic NECs activate these upstream effectors of the caspase cascade but fail to undergo apoptosis. Unlike to hMPV infection, treatment with a non-viral inducer of apoptosis induced strong activation of caspase-9 and -3/7 in NECs from asthmatics, thus demonstrating a virus-specific interaction that leads to defective apoptosis. These data suggest that viral-cellular interactions in NECs from asthmatic adults dictate cell survival or death and confer susceptibility to hMPV.
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Engin Baturcam (Herston, Australia), Engin Baturcam, Tiong Han Yeo, Johanna Schagen, Natale Snape, Emma Thomas, Janine Di-Masi, Sally Galbraith, Simon Phipps, Emmanuelle Fantino, Peter Sly, Kirsten Spann. Airway epithelial cells from asthmatic adults support elevated human metapneumovirus infection due to impaired apoptosis. Eur Respir J 2015; 46: Suppl. 59, 5034
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