title: Differential cytopathogenesis of respiratory syncytial virus prototypic and clinical isolates in primary pediatric bronchial epithelial cells.
abstract: BACKGROUND
  Human respiratory syncytial virus (RSV) causes severe respiratory disease in infants. Airway epithelial cells are the principle targets of RSV infection. However, the mechanisms by which it causes disease are poorly understood. Most RSV pathogenesis data are derived using laboratory-adapted prototypic strains. We hypothesized that such strains may be poorly representative of recent clinical isolates in terms of virus/host interactions in primary human bronchial epithelial cells (PBECs).
  
  
  METHODS
  To address this hypothesis, we isolated three RSV strains from infants hospitalized with bronchiolitis and compared them with the prototypic RSV A2 in terms of cytopathology, virus growth kinetics and chemokine secretion in infected PBEC monolayers.
  
  
  RESULTS
  RSV A2 rapidly obliterated the PBECs, whereas the clinical isolates caused much less cytopathology. Concomitantly, RSV A2 also grew faster and to higher titers in PBECs. Furthermore, dramatically increased secretion of IP-10 and RANTES was evident following A2 infection compared with the clinical isolates.
  
  
  CONCLUSIONS
  The prototypic RSV strain A2 is poorly representative of recent clinical isolates in terms of cytopathogenicity, viral growth kinetics and pro-inflammatory responses induced following infection of PBEC monolayers. Thus, the choice of RSV strain may have important implications for future RSV pathogenesis studies.
authors.affiliation: Centre for Infection & Immunity, School of Medicine, Dentistry & Biomedical Sciences, Queens University Belfast, Belfast BT9 7BL, Northern Ireland.
authors.forename: Rémi
authors.initials: R
authors.lastname: Villenave
authors.forename: Dara
authors.initials: D
authors.lastname: O'Donoghue
authors.forename: Surendran
authors.initials: S
authors.lastname: Thavagnanam
authors.forename: Olivier
authors.initials: O
authors.lastname: Touzelet
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Skibinski
authors.forename: Liam G
authors.initials: LG
authors.lastname: Heaney
authors.forename: James P
authors.initials: JP
authors.lastname: McKaigue
authors.forename: Peter V
authors.initials: PV
authors.lastname: Coyle
authors.forename: Michael D
authors.initials: MD
authors.lastname: Shields
authors.forename: Ultan F
authors.initials: UF
authors.lastname: Power
mesh_terms: D001990:Bronchiolitis, Viral / Q000821:virology; D018925:Chemokines / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003588:Cytopathogenic Effect, Viral; D004847:Epithelial Cells / Q000821:virology*; D006801:Humans; D007223:Infant; D020545:Respiratory Mucosa / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000821:virology*; D018113:Respiratory Syncytial Virus, Human / Q000254:growth & development / Q000302:isolation & purification* / Q000472:pathogenicity*; D014774:Virulence; D014779:Virus Replication
chemical_list: D018925:Chemokines