title: In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo.
abstract: Respiratory syncytial virus (RSV) is the major viral cause of severe pulmonary disease in young infants worldwide. However, the mechanisms by which RSV causes disease in humans remain poorly understood. To help bridge this gap, we developed an ex vivo/in vitro model of RSV infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs), the primary targets of RSV infection in vivo. Our RSV/WD-PBEC model demonstrated remarkable similarities to hallmarks of RSV infection in infant lungs. These hallmarks included restriction of infection to noncontiguous or small clumps of apical ciliated and occasional nonciliated epithelial cells, apoptosis and sloughing of apical epithelial cells, occasional syncytium formation, goblet cell hyperplasia/metaplasia, and mucus hypersecretion. RSV was shed exclusively from the apical surface at titers consistent with those in airway aspirates from hospitalized infants. Furthermore, secretion of proinflammatory chemokines such as CXCL10, CCL5, IL-6, and CXCL8 reflected those chemokines present in airway aspirates. Interestingly, a recent RSV clinical isolate induced more cytopathogenesis than the prototypic A2 strain. Our findings indicate that this RSV/WD-PBEC model provides an authentic surrogate for RSV infection of airway epithelium in vivo. As such, this model may provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines or therapeutics.
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences,  Queens University Belfast, Belfast BT9 7BL,  Northern Ireland.
authors.forename: Rémi
authors.initials: R
authors.lastname: Villenave
authors.forename: Surendran
authors.initials: S
authors.lastname: Thavagnanam
authors.forename: Severine
authors.initials: S
authors.lastname: Sarlang
authors.forename: Jeremy
authors.initials: J
authors.lastname: Parker
authors.forename: Isobel
authors.initials: I
authors.lastname: Douglas
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: D017209:Apoptosis; D001980:Bronchi / Q000473:pathology*; D002454:Cell Differentiation; D018925:Chemokines / Q000378:metabolism; D002648:Child; D002923:Cilia / Q000473:pathology; D003588:Cytopathogenic Effect, Viral; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015726:Giant Cells / Q000473:pathology / Q000821:virology; D020397:Goblet Cells / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D008954:Models, Biological; D009093:Mucus / Q000378:metabolism; D020545:Respiratory Mucosa / Q000473:pathology* / Q000821:virology*; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D018925:Chemokines