title: Relative respiratory syncytial virus cytopathogenesis in upper and lower respiratory tract epithelium.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) is a major pathogen that primarily infects airway epithelium. Most infants suffer mild upper respiratory tract (URT) symptoms, whereas approximately one-third progress to lower respiratory tract (LRT) involvement. Despite the ubiquity of URT infection, little is known about the relative cytopathogenesis of RSV infection in infant URT and LRT.
  
  
  OBJECTIVE
  This study aimed to compare RSV cytopathogenesis in nasal- and bronchial-derived epithelium from the same individuals using novel models derived from well-differentiated primary pediatric nasal (WD-PNECs) and bronchial epithelial cells (WD-PBECs).
  
  
  METHODS
  WD-PNECs and WD-PBECs were generated from nasal and bronchial brushes, respectively, and mock-infected or infected with RSV BT2a. RSV tropism, infectivity, cytopathology, growth kinetics, cell sloughing, apoptosis, and cytokine and chemokine responses were determined.
  
  
  RESULTS
  RSV infection in both cultures was restricted to apical ciliated cells and occasional nonciliated cells but not goblet cells. It did not cause gross cytopathology. Infection resulted in apical release of progeny virus, increased apical cell sloughing, apoptosis, and occasional syncytia. RSV growth kinetics and peak titers were higher in WD-PBECs, coincident with higher ciliated cell contents, cell sloughing, and slightly compromised tight junctions. However, proinflammatory chemokine responses were similar for both cultures. Also, lambda IFNs, especially IL-29, were induced by RSV infection.
  
  
  CONCLUSIONS
  RSV induced remarkably similar, albeit quantitatively lower, cytopathogenesis and proinflammatory responses in WD-PNECs compared with WD-PBECs that reproduce many hallmarks of RSV pathogenesis in infants. WD-PNECs may provide an authentic surrogate model with which to study RSV cytopathogenesis in infant airway epithelium.
authors: 1 Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast, Northern Ireland, United Kingdom.
authors: Hong
authors: H
authors: Guo-Parke
authors: Paul
authors: P
authors: Canning
authors: Isobel
authors: I
authors: Douglas
authors: Rémi
authors: R
authors: Villenave
authors: Liam G
authors: LG
authors: Heaney
authors: Peter V
authors: PV
authors: Coyle
authors: Jeremy D
authors: JD
authors: Lyons
authors: Michael D
authors: MD
authors: Shields
authors: Ultan F
authors: UF
authors: Power
mesh_terms: D001980:Bronchi / Q000276:immunology / Q000473:pathology / Q000821:virology*; D002454:Cell Differentiation; D018925:Chemokines / Q000276:immunology; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology; D003588:Cytopathogenic Effect, Viral / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D007494:Ireland; D009297:Nasal Mucosa / Q000276:immunology / Q000473:pathology / Q000821:virology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000473:pathology* / Q000821:virology; D012136:Respiratory Syncytial Viruses; D012141:Respiratory Tract Infections / Q000276:immunology / Q000473:pathology / Q000821:virology*; D014779:Virus Replication
chemical_list: D018925:Chemokines; D016207:Cytokines