In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

Rémi Villenave, Surendran Thavagnanam, Severine Sarlang, Jeremy Parker, Isobel Douglas, Grzegorz Skibinski, Liam G. Heaney, James P. McKaigue, Peter V. Coyle, Michael D. Shields, Ultan F. Power

Research output: Contribution to journalArticlepeer-review

131 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)5040-5050
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number13
Early online date12 Mar 2012
DOIs
Publication statusPublished - 27 Mar 2012

Keywords

  • primary airway epithelial cells
  • virus-host interaction
  • lung epithelium model
  • RSV

ASJC Scopus subject areas

  • General

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