Coxsackievirus entry into polarized endothelial cells triggers intracellular calcium depletion via decay-accelerating factor, requiring Src kinases, PLC, and IP3R3 to activate calpain-2.
The study identifies a specific calcium signaling pathway required for Group B coxsackievirus entry across polarized endothelial barriers, providing mechanistic insights into viral-induced heart disease and meningitis.
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.
Bozym et al. (Thu,) conducted a other in Coxsackievirus infection. Coxsackievirus (CVB) infection was evaluated on Intracellular calcium release and viral entry mechanisms. Coxsackievirus entry into polarized endothelial cells triggers intracellular calcium depletion via decay-accelerating factor, requiring Src kinases, PLC, and IP3R3 to activate calpain-2.
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