Cytopathogenesis of Sendai virus in well-differentiated primary pediatric bronchial epithelial cells

Remi Villenave, Olivier Touzelet, Surendran Thavagnanam, Severine Sarlang, Jeremy Parker, Grzegorz Skibinski, Liam Heaney, J.P. McKaigue, Peter Coyle, Michael Shields, Ultan Power

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Sendai virus (SeV) is a murine respiratory virus of considerable interest as a gene therapy or vaccine vector, as it is considered nonpathogenic in humans. However, little is known about its interaction with the human respiratory tract. To address this, we developed a model of respiratory virus infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs). These physiologically authentic cultures are comprised of polarized pseudostratified multilayered epithelium containing ciliated, goblet, and basal cells and intact tight junctions. To facilitate our studies, we rescued a replication-competent recombinant SeV expressing enhanced green fluorescent protein (rSeV/eGFP). rSeV/eGFP infected WD-PBECs efficiently and progressively and was restricted to ciliated and nonciliated cells, not goblet cells, on the apical surface. Considerable cytopathology was evident in the rSeV/eGFP-infected cultures postinfection. This manifested itself by ciliostasis, cell sloughing, apoptosis, and extensive degeneration of WD-PBEC cultures. Syncytia were also evident, along with significant basolateral secretion of proinflammatory chemokines, including IP-10, RANTES, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), interleukin 6 (IL-6), and IL-8. Such deleterious responses are difficult to reconcile with a lack of pathogenesis in humans and suggest that caution may be required in exploiting replication-competent SeV as a vaccine vector. Alternatively, such robust responses might constitute appropriate normal host responses to viral infection and be a prerequisite for the induction of efficient immune responses.
Original languageEnglish
Pages (from-to)11718-11728
Number of pages11
JournalJournal of Virology
Volume84
Issue number22
Early online date01 Sep 2010
DOIs
Publication statusPublished - Nov 2010

ASJC Scopus subject areas

  • Immunology
  • Virology

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