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Open Access Research

Involvement of intracellular free Ca2+ in enhanced release of herpes simplex virus by hydrogen peroxide

Emiko Arimoto1, Soichi Iwai1, Tetsuro Sumi1, Yuzo Ogawa2 and Yoshiaki Yura1*

Author Affiliations

1 Department of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Osaka, Japan

2 Department of Pathology, Osaka University Graduate School of Dentistry, Osaka, Japan

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Virology Journal 2006, 3:62  doi:10.1186/1743-422X-3-62

Published: 31 August 2006

Abstract

Background

It was reported that elevation of the intracellular concentration of free Ca2+ ([Ca2+]i) by a calcium ionophore increased the release of herpes simplex virus type 1 (HSV-1). Freely diffusible hydrogen peroxide (H2O2) is implied to alter Ca2+ homeostasis, which further enhances abnormal cellular activity, causing changes in signal transduction, and cellular dysfunction. Whether H2O2 could affect [Ca2+]i in HSV-1-infected cells had not been investigated.

Results

H2O2 treatment increased the amount of cell-free virus and decreased the proportion of viable cells. After the treatment, an elevation in [Ca2+]i was observed and the increase in [Ca2+]i was suppressed when intracellular and cytosolic Ca2+ were buffered by Ca2+ chelators. In the presence of Ca2+ chelators, H2O2-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 H2O2-treated cells.

Conclusion

These results indicate that H2O2 can elevate [Ca2+]i and induces non-apoptotic cell death with membrane lesions, which is responsible for the increased release of HSV-1 from epithelial cells.