Bcl-2 blocks accretion or depletion of stored calcium but has no effect on the redistribution of IP3 receptor I mediated by glycoprotein E of herpes simplex virus 1.
We examined the status of stable, resting intracellular Ca2+ ([Ca2+]i) and the calcium that can be released from intracellular stores in HEp-2 or VAX-3 cells overexpressing Bcl-2 after infection with wild-type or mutant herpes simplex viruses. The mutants included viruses lacking ICP4 or ICP27 and known to induce apoptosis. We report the following. Stable Ca2+ levels decrease after infection with wild-type or mutant viruses in both HEp-2 and VAX-3 cells. The histamine-sensitive calcium stores became depleted in wild-type and mutant virus-infected cells late in infection but increased significantly in DeltaICP4- or DeltaICP27-infected cells prior to depletion. In VAX-3 cells, the depletion in calcium stores did not take place as late as 24 h after infection, concomitant with lack of visually detectable cytopathic effects. Concurrent analyses showed that the amounts of IP3 Ca2+-receptor type I (IP3R-I) remained stable throughout infection, but the intensity of the signal increased and intracellular distribution changed dramatically in both HEp-2 and VAX-3 cells infected with the wild-type and all mutant viruses, except for the mutant lacking glycoprotein E (DeltagE). In transfected HEp-2 cells, gE and gI were more effective at augmenting the signal intensity and redistribution of IP3R-I than gE or gI alone. We conclude the following. (i) Depleted histamine-sensitive calcium stores correlate with appearance of cytopathic effects. (ii) Apoptosis, the calcium stores, and cytopathic effects are regulated by Bcl-2. (iii) The changes in the distribution of IP3R-I are mediated by the viral Fc receptor complex, but the redistribution is not related to changes in stored calcium.
Kalamvoki
Maria
M
The Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, 910 East 58th Street, Chicago, IL 60637, USA.
Roizman
Bernard
B
D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D006632:Histamine / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D007700:Kinetics; D008856:Microscopy, Fluorescence; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011961:Receptors, Fc / Q000737:chemistry / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism*
C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D019253:Proto-Oncogene Proteins c-bcl-2; D011961:Receptors, Fc; D014759:Viral Envelope Proteins; C044768:glycoprotein E, herpes simplex virus type 1; C048925:herpes simplex virus, type 1 protein ICP4; D006632:Histamine; D002118:Calcium