| Cytopathogenesis of Sendai virus in well-differentiated primary pediatric bronchial epithelial cells. | |
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MedLine Citation:
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PMID: 20810726 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-01 |
Journal Detail:
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Title: Journal of virology Volume: 84 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-26 Completed Date: 2010-11-22 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 11718-28 Citation Subset: IM |
Affiliation:
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Queen's University Belfast, Medical Biology Centre, Belfast BT9 7BL, Northern Ireland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Bronchi
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cytology*,
immunology,
pathology,
virology Cell Differentiation* Cells, Cultured Child Cytokines / immunology Cytopathogenic Effect, Viral Epithelial Cells / cytology, immunology, pathology, virology* Female Humans Male Respirovirus Infections / immunology, pathology, virology* Sendai virus / physiology* Virus Replication |
| Chemical | |
Reg. No./Substance:
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0/Cytokines |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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