The cytoplasmic mRNA which codes for the herpes simplex virus specific thymidine kinase (TK) is polyadenylated and is 14.5s in size. This corresponds to an RNA of 1400 nucleotides. The TK polypeptide is about 42,000 daltons, which requires 1100 nucleotide. We conclude that the cytoplasmic mRNA is monocistronic. The reticulocyte lysate cell-free translation system synthesizes enzymatically activ...

The connexin 26 (Cx26) gene suppresses the growth of HeLa cells in vitro and in vivo. We explored the possibility that the Cx26 gene not only suppresses growth but can also mediate the bystander effect that is observed in some gene therapy. In gene therapy mediated by the herpes simplex virus thymidine kinase, the toxicity of ganciclovir affects not only the cells transduced with the gene but a...

5 -O-Trityl derivatives of thymidine (dThd), (E)-5-(2-bromovinyl)-2 -deoxyuridine (BVDU), and their acyclic analogs 1-[(Z)-4triphenylmethoxy-2-butenyl]thymine (KIN-12) and (E)-5-(2-bromovinyl)-1-[(Z)-4-triphenylmethoxy-2-butenyl]uracil (KIN-52) have been synthesized and evaluated for their inhibitory activity against the amino acid sequence related mitochondrial dThd kinase (TK-2), herpes simpl...

Plasma thymidine kinase (TK) activity was evaluated as a plasma marker for canine lymphoma and leukemia. A tentative "cut-off" value was set at 6.0 U/l as the upper level of plasma TK based on the mean + 2SD of plasma TK activity in 13 clinically healthy dogs. The levels of plasma TK activity in all of the 20 dogs with lymphoma and leukemia were higher than the cut-off value, whereas those in d...

Glucocorticoids are released in response to stressful experiences and serve many beneficial homeostatic functions. However, dysregulation of glucocorticoids is associated with cognitive impairments and depressive illness. In the hippocampus, a brain region densely populated with receptors for stress hormones, stress and glucocorticoids strongly inhibit adult neurogenesis. Decreased neurogenesis...

A single-cytosine-deletion in the herpes simplex virus gene encoding thymidine kinase (TK) was previously found in an acyclovir-resistant clinical isolate. A laboratory strain engineered to carry this mutation did not generate sufficient TK activity for detection by plaque autoradiography, which detected 0.25% wild-type activity. However, a drug sensitivity assay suggested that extremely low le...

A HeLa cell transient-expression assay system was used to determine if isolated immediate early (alpha) genes from herpes simplex virus (HSV) could transcriptionally activate (transactivate) the type 1 (HSV-1) thymidine kinase (TK) gene [an early (beta) gene]. Cells transfected with the TK gene alone transcribed very low levels of TK RNA. Cells cotransfected with plasmids bearing the sequences ...

In this report, we describe the cloning of the human cytoplasmic thymidine kinase (tk-C; EC 2.7.1.21) gene and its preliminary characterization. The tk-C sequences were isolated from a phage genomic library made from DNA of a transfected mouse cell carrying the human tk-C gene. The human transforming sequences were identified by homology with human Alu sequences. Six recombinant phages were iso...

Recently, an entirely new class of bicyclic nucleoside analogs (BCNAs) was found to display exquisite potency and selectivity as inhibitors of varicella-zoster virus (VZV) replication in cell culture. A striking difference in their ability to convert the BCNAs to their phosphorylated derivatives was observed between the VZV-encoded thymidine kinase (TK) and the very closely related herpes simpl...

Previous work from our laboratory suggested that the selective inhibition of Epstein-Barr virus (EBV) replication by 1-beta-D-arabinofuranosylthymine in human lymphoid cell lines involved the induction of a new thymidine kinase (TK) able to phosphorylate the thymidine analog. We further characterized this enzyme induced in various EBV-positive cell lines after viral genome activation with a com...