Abstract
Respiratory syncytial virus (RSV) is a major cause of respiratory disease. There are conflicting accounts of the response of human epithelial cells to RSV and a lack of data on its effect on ciliary function. Our aim was to study the early stages of RSV infection of primary human basal and ciliated cultures.
Using high speed video microscopy, we found that ciliary beat frequency was unaffected by RSV infection over 72 hours, however, ciliary dyskinesia significantly (P<0.05) increased within 24 hours of infection. Transmission electron microscopy revealed that ultrastructural abnormalities were confined to ciliated cells, including increased cilia loss and mitochondrial damage. Confocal immunofluorescence microscopy showed RSV antigen gradually spread from the cell surface to the ciliary tip of infected cells over three days. Interestingly, ciliated cultures secreted fewer viruses than basal (progenitor) cell cultures and produced a chemokine response focused on recruitment of neutrophils.
This study highlights differences in infection models and underscores the need to further to explore the role of ciliated cells in the establishment of RSV infection. Increased ciliary dyskinesia combined with ciliary loss and epithelial damage is likely to result in reduced mucociliary clearance early in the infective process.
- ERS