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Title page for ETD etd-11222013-202938

Type of Document Dissertation
Author Lai, Caroline Ming-Hwei
URN etd-11222013-202938
Title Endothelial JAM-A Facilitates Reovirus Bloodstream Spread
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Christopher R. Aiken Committee Chair
Ambra Pozzi Committee Member
John V. Williams Committee Member
Luc Van Kaer Committee Member
Terence S. Dermody Committee Member
  • hematogenous spread
  • viremia
  • endothelial cells
  • viral pathogenesis
  • reovirus
Date of Defense 2013-09-18
Availability unrestricted
Bloodstream spread is an essential step in the pathogenesis of many viruses. However,

mechanisms that promote viremia are not well understood. Reoviruses are neurotropic viruses

that disseminate systemically through the circulatory system. Junctional adhesion molecule-A

(JAM-A) serves as a receptor for reovirus and is expressed in tight junctions and on

hematopoietic cells. In infected mice, JAM-A is required for reovirus spread to sites of

secondary replication. To examine functions of endothelial and hematopoietic JAM-A in

reovirus bloodstream dissemination, I generated mice with altered JAM-A expression in these

cell types and assessed systemic reovirus spread. Endothelial but not hematopoietic JAM-A

facilitates reovirus bloodstream entry and egress. To determine how reovirus traverses

endothelia, I examined reovirus infection of polarized endothelial cells (ECs). Reovirus infection of polarized ECs is JAM-A-dependent but does not alter tight junction integrity. Viral release occurs exclusively from the luminal surface in the absence of cell lysis. These data implicate the endothelium as an important mediator of viral pathogenesis. Understanding hematogenous viral spread may aid in development of therapeutics that inhibit this key step in viral pathogenesis.

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