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Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Query: EC:2.7.7.7 (
DNA polymerase
)
17,007
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
It has been demonstrated both in vivo and in vitro that cytomegalovirus regulates not only MHC class I but also
class II antigen
expression on vascular endothelial cells. The CMV-linked MHC induction is believed to be involved in acute rejection mechanisms and chronic vasculopathy after transplantation. In this study, we have investigated the effect of 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG; ganciclovir) on CMV-induced class II expression in cultured rat heart microvascular endothelial cells. Two sets of cultured endothelial cells were infected with rat CMV. One of the sets was treated with various concentrations of DHPG and the other set was left untreated. MHC class II antigen expression on the cells was demonstrated by mAbs, by immunoperoxidase (IP) technique, and by FACS. Class II expression was maximal on CMV-infected cells 4-7 days after infection when 77.5 +/- 14.5% of the endothelial cells expressed class II in IP staining. DHPG inhibited the induction of class II, but the inhibitory effect was dependent upon the drug concentration. With increasing concentrations of DHPG (0, 1, 10, 100, and 1000 micrograms/ml), as demonstrated by IP staining (surface and intracellular expression), the frequency of class II-positive cells decreased from 77.5 +/- 14.5% to 58.0 +/- 15.0%, 36.0 +/- 23.0%, 3.0 +/- 3.0%, and 0 +/- 0%, respectively. By FACS (surface expression), the number of class II-positive cells remained somewhat lower, but decreased similarly with increasing concentrations of DHPG (from 37.8 +/- 1.1% to 6.2 +/- 3.1%) (surface expression). Also, the intensity of expression decreased concomitantly. These results suggest that DHPG inhibits CMV-induced class II expression via inhibition of CMV
DNA polymerase
.
...
PMID:Direct induction of class II molecules by cytomegalovirus in rat heart microvascular endothelial cells is inhibited by ganciclovir (DHPG). 797 30
Cytomegalovirus (CMV) has been demonstrated to induce
class II antigen
expression in endothelial cells. To study whether ganciclovir (DHPG) has an effect on CMV-induced class II expression, cultured rat heart endothelial cells were infected with rat CMV (RCMV) and treated with different DHPG concentrations. Class II antigens in endothelial cells were detected by a monoclonal antibody and immunoperoxidase technique. Control cells did not express
class II antigen
, but during RCMV infection 92% of cells were class II-positive. DHPG treatment (1, 10, 100 and 1000 microg/ml) decreased RCMV-induced class II expression from 73% to 59%, 6% and 0%, respectively. As DHPG inhibits CMV
DNA polymerase
, our present results suggest that DHPG affects RCMV-induced class II expression via the inhibition of RCMV DNA replication.
...
PMID:Induction of class II molecules by cytomegalovirus in rat heart endothelial cells is inhibited by ganciclovir. 1127 Dec 58