title: Ciliary dyskinesia is an early feature of respiratory syncytial virus infection.
abstract: Respiratory syncytial virus is a major cause of respiratory disease. There are conflicting accounts of the response of human epithelial cells to respiratory syncytial virus and a lack of data on its effect on ciliary function. Our aim was to study the early stages of respiratory syncytial virus infection of primary human basal and ciliated cultures. Using high speed videomicroscopy, we found that ciliary beat frequency was unaffected by respiratory syncytial virus infection over 72 h; however, ciliary dyskinesia significantly increased within 24 h of infection (p<0.05). Transmission electron microscopy revealed that ultrastructural abnormalities were confined to ciliated cells, including increased cilia loss and mitochondrial damage. Confocal immunofluorescence microscopy showed that respiratory syncytial virus antigen gradually spread from the cell surface to the ciliary tip of infected cells over 3 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 explore further the role of ciliated cells in the establishment of respiratory syncytial virus infection. Increased ciliary dyskinesia combined with ciliary loss and epithelial damage is likely to result in reduced mucociliary clearance early in the infective process.
authors.affiliation: Portex Unit, University College London, Institute of Child Health, London.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Smith
authors.forename: Hemant
authors.initials: H
authors.lastname: Kulkarni
authors.forename: Priya
authors.initials: P
authors.lastname: Radhakrishnan
authors.forename: Andrew
authors.initials: A
authors.lastname: Rutman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bankart
authors.forename: Gwyneth
authors.initials: G
authors.lastname: Williams
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hirst
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Easton
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
authors.forename: Chris
authors.initials: C
authors.lastname: O'Callaghan
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000378:metabolism; D002478:Cells, Cultured; D002923:Cilia / Q000502:physiology; D002925:Ciliary Motility Disorders / Q000175:diagnosis*; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D018715:Microscopy, Video; D008875:Middle Aged; D009079:Mucociliary Clearance; D018357:Respiratory Syncytial Virus Infections / Q000175:diagnosis*; D012136:Respiratory Syncytial Viruses; D018417:Th1 Cells / Q000166:cytology; D055815:Young Adult
chemical_list: D000956:Antigens, Viral