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


CONCLUSIONS
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.
Arimoto
Emiko
E
Department of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Osaka, Japan. arimoto@tenriyorozu-hp.or.jp
Iwai
Soichi
S
Sumi
Tetsuro
T
Ogawa
Yuzo
Y
Yura
Yoshiaki
Y
D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication; D016923:Cell Death; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D053938:DNA Fragmentation; D004533:Egtazic Acid / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000648:ultrastructure / Q000821:virology*; D005434:Flow Cytometry; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*
D002614:Chelating Agents; D004533:Egtazic Acid; D006861:Hydrogen Peroxide; D002118:Calcium