Involvement of intracellular free Ca(2+ )in enhanced release of herpes simplex virus by hydrogen peroxide

BACKGROUND: It was reported that elevation of the intracellular concentration of free Ca(2+ )([Ca(2+)]i) by a calcium ionophore increased the release of herpes simplex virus type 1 (HSV-1). Freely diffusible hydrogen peroxide (H(2)O(2)) is implied to alter Ca(2+ )homeostasis, which further enhances abnormal cellular activity, causing changes in signal transduction, and cellular dysfunction. Whether H(2)O(2 )could affect [Ca(2+)]i in HSV-1-infected cells had not been investigated. RESULTS: H(2)O(2 )treatment increased the amount of cell-free virus and decreased the proportion of viable cells. After the treatment, an elevation in [Ca(2+)]i was observed and the increase in [Ca(2+)]i was suppressed when intracellular and cytosolic Ca(2+ )were buffered by Ca(2+ )chelators. In the presence of Ca(2+ )chelators, H(2)O(2)-mediated increases of cell-free virus and cell death were also diminished. Electron microscopic analysis revealed enlarged cell junctions and a focal disintegration of the plasma membrane in H(2)O(2)-treated cells. CONCLUSION: These results indicate that H(2)O(2 )can elevate [Ca(2+)]i and induces non-apoptotic cell death with membrane lesions, which is responsible for the increased release of HSV-1 from epithelial cells.