Junctional Adhesion Molecule-A Is Required for Hematogenous Dissemination of Reovirus

Annukka A.R. Antar, Jennifer L. Konopka, Jacquelyn A. Campbell, Rachel A. Henry, Ana L. Perdigoto, Bruce D. Carter, Ambra Pozzi, Ty W. Abel, Terence S. Dermody

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)59-71
Number of pages13
JournalCell Host and Microbe
Volume5
Issue number1
DOIs
StatePublished - Jan 22 2009
Externally publishedYes

Keywords

  • CELLBIO
  • MICROBIO

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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    Antar, A. A. R., Konopka, J. L., Campbell, J. A., Henry, R. A., Perdigoto, A. L., Carter, B. D., Pozzi, A., Abel, T. W., & Dermody, T. S. (2009). Junctional Adhesion Molecule-A Is Required for Hematogenous Dissemination of Reovirus. Cell Host and Microbe, 5(1), 59-71. https://doi.org/10.1016/j.chom.2008.12.001