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 decayaccelerating 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. © 2010 bozym et al.