Document Detail


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.
MedLine Citation:
PMID:  2982353     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
H Meijer; C A Bruggeman; P H Dormans; C P van Boven
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Archives of virology     Volume:  83     ISSN:  0304-8608     ISO Abbreviation:  Arch. Virol.     Publication Date:  1985  
Date Detail:
Created Date:  1985-03-14     Completed Date:  1985-03-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7506870     Medline TA:  Arch Virol     Country:  AUSTRIA    
Other Details:
Languages:  eng     Pagination:  181-94     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acyclovir / pharmacology*
Animals
Bromodeoxyuridine / pharmacology
Cell Division
Cells, Cultured
Cytomegalovirus / drug effects,  growth & development,  physiology*
Cytosol / enzymology
Deoxycytidine Kinase / biosynthesis*,  metabolism
Electrophoresis, Polyacrylamide Gel
Enzyme Induction
Fibroblasts
Interphase
Phosphotransferases / antagonists & inhibitors,  biosynthesis*,  metabolism
Phosphotransferases (Alcohol Group Acceptor)*
Rats
Substrate Specificity
Thymidine Kinase / biosynthesis*,  metabolism
Chemical
Reg. No./Substance:
59-14-3/Bromodeoxyuridine; 59277-89-3/Acyclovir; EC 2.7.-/Phosphotransferases; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.113/deoxyguanosine kinase; EC 2.7.1.21/Thymidine Kinase; EC 2.7.1.74/Deoxycytidine Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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