Endothelial JAM-A Facilitates Reovirus Bloodstream Spread
Lai, Caroline Ming-Hwei
:
2013-12-04
Abstract
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.