Human cytomegalovirus modulates the Ca2+ response to vasopressin and ATP in fibroblast cultures.
The free calcium concentrations in the nucleus ([Ca2+]n) and in cytosol ([Ca2+]c) of cultured human embryonic lung (HEL) fibroblasts were estimated by confocal laser microscopy using the Ca(2+)-indicator Indo-1. In resting HEL cells, The free cellular Ca(2+)-concentration significantly increased upon human cytomegalovirus (HCMV) infection. The ratio between [Ca2+]n and [Ca2+]c was not affected. Following stimulation by ATP or [Arg8] vasopressin (AVP), a differential Ca2+ response of the HCMV-infected HEL cells was observed. While uninfected cells were highly sensitive to AVP and only poorly sensitive to ATP, infected cells showed a high responsiveness to ATP but not to AVP. This switch in sensitivity to the agonists first observed at 24 h post infection. The Ca(2+)-rise following ATP or AVP stimulation was derived from intracellular Ca2+ stores. The magnitude of the ATP-induced Ca(2+)-rise increased upon infection. In contrast to non-infected cells where [Ca2+]n > [Ca2+]c during stimulation with AVP or ATP, no nucleo-cytosolic Ca(2+)-gradient was observed in infected cells. Furthermore, the magnitude of the Ca2+ rise in the two compartments was higher in ATP-stimulated cells. It is concluded that HCMV infection significantly interferes with Ca(2+)-homeostasis in HEL cells which could be related to the pathogenesis of the disease.
Himpens
B
B
Physiological Laboratory, Faculty of Medicine, Katholieke Universiteit Leuven, Belgium.
Proot
P
P
Neyts
J
J
De Smedt
H
H
De Clercq
E
E
Casteels
R
R
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D003587:Cytomegalovirus / Q000254:growth & development*; D005333:Fetus / Q000166:cytology / Q000821:virology; D005347:Fibroblasts / Q000166:cytology / Q000821:virology; D005434:Flow Cytometry; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D008856:Microscopy, Fluorescence
D001127:Arginine Vasopressin; D000255:Adenosine Triphosphate; D002118:Calcium