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Title page for ETD etd-12052008-163459


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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