期刊
CELL HOST & MICROBE
卷 5, 期 1, 页码 59-71出版社
CELL PRESS
DOI: 10.1016/j.chom.2008.12.001
关键词
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资金
- Public Health Service [T32 GM07347, T32 CA09385, R37 AI38296, P30 CA68485]
- Elizabeth B. Lamb Center for Pediatric Research
- Vanderbilt Diabetes Research and Training Center [DK20593]
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.
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