Rat cytomegalovirus induces cellular purine and pyrimidine nucleoside kinases in rat embryo fibroblasts and TK- rat-2 cells. Correlations with the antiviral activity of Acyclovir.
Rat cytomegalovirus (RCMV) induces a cytosol thymidine kinase (TK) in G0-phase rat embryo fibroblasts (REF), but not in a TK deficient rat cell line (R-2), though virus titers in both cell types reached comparable levels. The results indicate that TK is neither virus-coded nor is required for a productive infection in R-2 cells. A deoxycytidine kinase (dCK) is induced in either growing or RCMV-infected REF and R-2 cells, suggesting that dCK is essential for both host-cell and viral DNA synthesis. A deoxyguanosine kinase (dGK) is detectable in low concentrations in either growing or G0-phase REF and R-2 cells suggesting that this enzyme is cell-cycle independent. In contrast, RCMV induces high persisting levels of dGK, particularly in R-2 cells, indicating that this enzyme is of crucial importance for viral DNA synthesis. By comparison of thermostabilities and electrophoretic mobilities (Rf for TK, dCK and dGK were 0.12; 0.97; and 0.54, respectively) the enzymes were found to be substrate specific but of cellular origin. In contrast to TK and dCK, only dGK is inhibited by Acyclovir (Ki = 320 microM). It is suggested that RCMV inducable dGK is an important enzyme determining the in vitro anti-CMV activity of Acyclovir.
Meijer
H
H
Bruggeman
C A
CA
Dormans
P H
PH
van Boven
C P
CP
D000212:Acyclovir / Q000494:pharmacology*; D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D003600:Cytosol / Q000201:enzymology; D003842:Deoxycytidine Kinase / Q000096:biosynthesis* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D005347:Fibroblasts; D007399:Interphase; D010770:Phosphotransferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor); D051381:Rats; D013379:Substrate Specificity; D013937:Thymidine Kinase / Q000096:biosynthesis* / Q000378:metabolism
D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C019165:deoxyguanosine kinase; D013937:Thymidine Kinase; D003842:Deoxycytidine Kinase; D001973:Bromodeoxyuridine; D000212:Acyclovir