Junctional adhesion molecule-A is required for hematogenous dissemination of reovirus.

Antar AA, Konopka JL, Campbell JA, Henry RA, Perdigoto AL, Carter BD, Pozzi A, Abel TW, Dermody TS
Cell Host Microbe. 2009 5 (1): 59-71

PMID: 19154988 · PMCID: PMC2642927 · DOI:10.1016/j.chom.2008.12.001

Diverse families of viruses bind immunoglobulin superfamily (IgSF) proteins located in tight junctions (TJs) 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 protein that localizes to TJs and serves as a receptor for mammalian reovirus. We inoculated wild-type (WT) and isogenic JAM-A(-/-) mice perorally with reovirus and found that JAM-A is dispensable for viral replication in the intestine but required for systemic dissemination. Reovirus replication in the brain and tropism for discrete neural regions are equivalent in WT and JAM-A(-/-) mice following intracranial inoculation, suggesting a function for JAM-A in reovirus spread to extraintestinal sites. JAM-A promotes reovirus infection of endothelial cells, providing a conduit for the virus into the bloodstream. These findings indicate that a broadly expressed IgSF viral receptor specifically mediates hematogenous dissemination in the host.

MeSH Terms (17)

Animals Body Weight Brain Cell Adhesion Molecules Endothelial Cells Heart Intestines Liver Mice Mice, Inbred C57BL Mice, Knockout Receptors, Cell Surface Receptors, Virus Reoviridae Reoviridae Infections Survival Analysis Virus Replication

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