Infection of human endothelium in vitro by cytomegalovirus causes enhanced expression of purinergic receptors: a potential virus escape mechanism?
BACKGROUND
Human cytomegalovirus (CMV) uses different strategies to escape from human host defense reactions. Previously we have observed that infection of endothelial cells with CMV in vitro leads to enhanced activity of endothelial ectonucleotidases. These ectoenzymes are responsible for hydrolysis of extracellular adenine nucleotides, resulting in the formation of adenosine. Infection with CMV in vivo therefore may result in local increase of adenosine production, providing an anti-inflammatory and antiaggregatory microenvironment, which may facilitate entry of the virus into the target cell.


METHODS
The present study focuses on the expression of P2 type purinergic receptors on endothelial cells after infection with CMV. Human endothelial cells were infected with CMV and compared with either uninfected cells or endothelial cells infected with other herpesviruses (herpes simplex virus [HSV] 1 or 2) for the expression of P2 receptors such as P2Y1, P2Y2, or P2X7. For comparison, cells stimulated with nonspecific agents were also studied.


RESULTS
A strong upregulation of the P2 receptors tested was shown, exclusively in CMV-infected cells. Stimulation with either HSV-1 or HSV2, nonspecific stimulants, or various cytokines did not affect the expression of these P2 receptors significantly.


CONCLUSIONS
Infection of endothelium with CMV causes significant upregulation of the P2 receptors studied. As these receptors may potentially be able to concentrate nucleotides along the ectonucleotidases of the endothelial cell membrane, rapid local hydrolysis of adenosine triphosphate and adenosine diphosphate may be facilitated by enhanced P2 receptor expression. Such a CMV induced mechanism might enable the virus to escape from an important host defense response, such as local microthrombus formation.
Department of Internal Medicine, Division of Nephrology, Groningen University Medical Center, Groningen, The Netherlands. marietzandberg@hotmail.com
Mariët
M
Zandberg
Willem J
WJ
van Son
Martin C
MC
Harmsen
Winston W
WW
Bakker
D003587:Cytomegalovirus / Q000472:pathogenicity*; D004730:Endothelium, Vascular / Q000821:virology*; D005786:Gene Expression Regulation; D006801:Humans; D011983:Receptors, Purinergic / Q000235:genetics*; D018139:Simplexvirus / Q000472:pathogenicity; D014470:Umbilical Cord / Q000821:virology; D014471:Umbilical Veins
D011983:Receptors, Purinergic