Induction and antagonism of antiviral responses in respiratory syncytial virus-infected pediatric airway epithelium.

Remi Villenave, Lindsay Broadbent, Isobel Douglas, Jeremy D. Lyons, Peter V. Coyle, Michael N. Teng, Ralph A. Tripp, Liam G. Heaney, Michael D. Shields, Ultan F. Power

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)
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Abstract

Airway epithelium is the primary target of many respiratory viruses. However, virus induction and antagonism of host responses by human airway epithelium remains poorly understood. To address this, we developed a model of respiratory syncytial virus (RSV) infection based on well- differentiated pediatric primary bronchial epithelial cell cultures (WD-PBECs) that mimics hallmarks of RSV disease in infants. RSV is the most important respiratory viral pathogen in young infants worldwide. We found that RSV induces a potent antiviral state in WD-PBECs that was mediated in part by secreted factors, including interferon lambda-1 (IFNλ1)/IL-29. In contrast, type I interferons were not detected following RSV infection of WD-PBECs., Interferon (IFN) responses in RSV-infected WD-PBECs reflected those in lower airway samples from RSV-hospitalized infants. In view of the prominence of IL-29, we determined whether recombinant IL-29 treatment of WD-PBECs before or after infection abrogated RSV replication. Interestingly, IL-29 demonstrated prophylactic, but not therapeutic, potential against RSV. The absence of therapeutic potential reflected effective RSV antagonism of IFN-mediated antiviral responses in infected cells. Our data are consistent with RSV non-structural proteins 1 and/or 2 perturbing the Jak-STAT signaling pathway, with concomitant reduced expression of antiviral effector molecules, such as MxA/B. Antagonism of Jak-STAT signaling was restricted to RSV-infected cells in WD-PBEC cultures. Importantly, our study provides the rationale to further explore IL-29 as a novel RSV prophylactic.
Original languageEnglish
Pages (from-to)12309-12318
Number of pages10
JournalJournal of Virology
Volume89
Issue number24
Early online date30 Sep 2015
DOIs
Publication statusPublished - Dec 2015

Keywords

  • Animals
  • Cercopithecus aethiops
  • Humans
  • Infant
  • Interleukins/immunology
  • Janus Kinases/immunology
  • Myxovirus Resistance Proteins/immunology
  • Respiratory Mucosa/immunology
  • Respiratory Syncytial Virus Infections/immunology
  • Respiratory Syncytial Virus, Human/immunology
  • STAT Transcription Factors/immunology
  • Signal Transduction/drug effects
  • Vero Cells

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