Cytopathogenesis of Sendai Virus in Well-Differentiated Primary Pediatric Bronchial Epithelial Cells
| Autor: | Ultan F. Power, Severine Sarlang, James P. McKaigue, Peter V. Coyle, Olivier Touzelet, Surendran Thavagnanam, Grzegorz Skibinski, Michael D. Shields, Remi Villenave, Liam G Heaney, JC Parker |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Paramyxoviridae Immunology Bronchi Virus Replication Respirovirus Infections Sendai virus Microbiology Virus Immune system Cytopathogenic Effect Viral Virology Humans Interleukin 8 Child Mononegavirales Cells Cultured Syncytium biology Cell Differentiation Epithelial Cells biology.organism_classification Virus-Cell Interactions Insect Science Cytokines Respiratory virus Female |
| Zdroj: | Journal of Virology. 84:11718-11728 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.00798-10 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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