Document Detail

Cytopathogenesis of Sendai virus in well-differentiated primary pediatric bronchial epithelial cells.
MedLine Citation:
PMID:  20810726     Owner:  NLM     Status:  MEDLINE    
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.
Rémi Villenave; Olivier Touzelet; Surendran Thavagnanam; Severine Sarlang; Jeremy Parker; Grzegorz Skibinski; Liam G Heaney; James P McKaigue; Peter V Coyle; Michael D Shields; Ultan F Power
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-01
Journal Detail:
Title:  Journal of virology     Volume:  84     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-26     Completed Date:  2010-11-22     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11718-28     Citation Subset:  IM    
Queen's University Belfast, Medical Biology Centre, Belfast BT9 7BL, Northern Ireland.
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MeSH Terms
Bronchi / cytology*,  immunology,  pathology,  virology
Cell Differentiation*
Cells, Cultured
Cytokines / immunology
Cytopathogenic Effect, Viral
Epithelial Cells / cytology,  immunology,  pathology,  virology*
Respirovirus Infections / immunology,  pathology,  virology*
Sendai virus / physiology*
Virus Replication
Reg. No./Substance:

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