Release of intracellular calcium stores facilitates coxsackievirus entry into polarized endothelial cells.
Group B coxsackieviruses (CVB) are associated with viral-induced heart disease and are among the leading causes of aseptic meningitis worldwide. Here we show that CVB entry into polarized brain microvasculature and aortic endothelial cells triggers a depletion of intracellular calcium stores initiated through viral attachment to the apical attachment factor decay-accelerating factor. Calcium release was dependent upon a signaling cascade that required the activity of the Src family of tyrosine kinases, phospholipase C, and the inositol 1,4,5-trisphosphate receptor isoform 3. CVB-mediated calcium release was required for the activation of calpain-2, a calcium-dependent cysteine protease, which controlled the vesicular trafficking of internalized CVB particles. These data point to a specific role for calcium signaling in CVB entry into polarized endothelial monolayers and highlight the unique signaling mechanisms used by these viruses to cross endothelial barriers.
Duke Scholars
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Related Subject Headings
- Virus Internalization
- Virology
- Phospholipase C gamma
- Intracellular Space
- Inositol 1,4,5-Trisphosphate Receptors
- Humans
- Epithelium
- Enterovirus
- Endothelium, Vascular
- Endothelial Cells
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Virus Internalization
- Virology
- Phospholipase C gamma
- Intracellular Space
- Inositol 1,4,5-Trisphosphate Receptors
- Humans
- Epithelium
- Enterovirus
- Endothelium, Vascular
- Endothelial Cells