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

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

author email corresponding author email

Virology Journal 2006, 3:62doi: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.