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

被引:100
作者
Antar, Annukka A. R. [1 ,2 ]
Konopka, Jennifer L. [2 ,3 ]
Campbell, Jacquelyn A. [1 ,2 ]
Henry, Rachel A. [1 ]
Perdigoto, Ana L. [4 ,5 ]
Carter, Bruce D. [4 ,5 ]
Pozzi, Ambra [6 ,7 ,8 ]
Abel, Ty W. [9 ]
Dermody, Terence S. [1 ,2 ,3 ]
机构
[1] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA
[5] Vanderbilt Univ, Sch Med, Ctr Mol Neurosci, Nashville, TN 37232 USA
[6] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA
[7] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA
[8] Vet Affairs Hosp, Dept Med, Nashville, TN 37212 USA
[9] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA
关键词
CENTRAL-NERVOUS-SYSTEM; ATTACHMENT PROTEIN SIGMA-1; TYPE-3; REOVIRUS; SIALIC-ACID; RECEPTOR; ENTRY; INFECTION; GROWTH; CELLS; DETERMINES;
D O I
10.1016/j.chom.2008.12.001
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:59 / 71
页数:13
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