| Type of Document |
Dissertation |
| Author |
Antar, Annukka Aida Rose
|
| URN |
etd-12052008-163459 |
| Title |
Junctional Adhesion Molecule-A and Reovirus Pathogenesis |
| Degree |
PhD |
| Department |
Microbiology and Immunology |
| Advisory Committee |
| Advisor Name |
Title |
| Christopher Aiken |
Committee Chair |
| Earl Ruley |
Committee Member |
| Ethan Lee |
Committee Member |
| Mark Denison |
Committee Member |
| Terence Dermody |
Committee Member |
|
| Keywords |
- viral pathogenesis
- junctional adhesion molecule-A
- JAM-A
- reovirus receptor
- Reoviruses
- tight junction viral receptor
- Cell adhesion molecules
- Virus diseases -- Pathogenesis
|
| Date of Defense |
2008-09-05 |
| Availability |
unrestricted |
Abstract
Diverse families of viruses bind immunoglobulin superfamily (IgSF) proteins located in tight junctions and adherens junctions of epithelium and endothelium. However, little is known about the roles of these receptors in the pathogenesis of viral disease. Junctional adhesion molecule-A (JAM-A) is an IgSF member that localizes to tight junctions and serves as a receptor for mammalian reovirus. Peroral inoculation of wild-type and isogenic JAM-A-/- mice demonstrated that JAM-A is dispensable for viral replication in the intestine but required for high-titer viremia and virus-induced encephalitis. Reovirus replication in the brain and tropism for discrete regions in neural tissues are equivalent in wild-type and JAM-A-/- mice following intracranial inoculation, suggesting a function for JAM-A in reovirus dissemination from the intestine. Hematogenous but not neural routes of reovirus dissemination are blunted in JAM-A-/- mice, and infection of neurons is JAM-A-independent, suggesting that JAM-A promotes dissemination of reovirus through the blood. JAM-A promotes reovirus infection of endothelial cells, providing a conduit for the virus into the bloodstream. These findings suggest a role for junction-associated viral receptors in hematogenous dissemination.
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| Files |
| Filename |
Size |
Approximate Download Time
(Hours:Minutes:Seconds)
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| 28.8 Modem |
56K Modem |
ISDN (64 Kb) |
ISDN (128 Kb) |
Higher-speed Access |
| |
AntarThesis120708.pdf |
5.63 Mb |
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