Infection of Vero cells with herpes simplex virus (HSV) causes a marked increase in the dTTP pool size of infected cells. In this study we examined the relative importance of the HSV-encoded ribonucleotide reductase (RR) and thymidine kinase (TK) in the increase of dTTP. In cells infected with an RR deletion mutant of HSV-1 strain KOS, there was no significant increase in the size of the dTTP p...

Herpes simplex virus (HSV) strain 1737, acyclovir-resistant and uniformly thymidine kinase-deficient (tkD) by all conventional assays, clinically reactivated in an AIDS patient in the absence of antiviral drug pressure. Investigation of its neurovirulence and latency characteristics in a mouse model using a tkD plaque isolate (1737-14), however, yielded a neurovirulent, homogeneous, acyclovir-s...

Gene therapy using the herpes simplex virus thymidine kinase gene (HSV-TK) is a promising new approach for the treatment of gliomas, a tumor type with a poor prognosis. To limit the toxic effects of this procedure, it is desirable to restrict expression of the HSV-TK gene to the target cells. This can be accomplished by use of the promoter of the glial fibrillary acidic protein gene, an interme...

To determine whether thymidine kinase (TK) isozyme status adds clinically useful information in adult nonHodgkin’s lymphoma (NHL). we have analyzed peripheral blood plasma and lymphocytes of 44 patients with NHL for either TK1 or TK2 isozyme activity. On the basis of isozyme status. patients could be divided into two groups that did not differ significantly with respect to known determinants fo...

Herpes simplex virus type-1 (HSV-1) is a neurotropic pathogen of humans that establishes latent infection in the sensory ganglia innervating the site of primary infection. A number of genes control HSV-1 pathogenicity and latency. Open reading frame P (ORF P) is one of these genes that might have a role in latency and pathogenesis. A complication in the analysis of the role of ORF P in the HSV-...

Thymidine kinase (TK), encoded by EBV (Epstein-Barr virus), is an attractive target for antiviral therapy and provides a novel approach to the treatment of EBV-associated malignancies. Despite the extensive use of nucleoside analogues for the treatment of viral infections and cancer, the structure-function relationship of EBV TK has been addressed rarely. In the absence of any structural inform...

We studied the effects of double-strand breaks on intramolecular extrachromosomal homologous recombination in mammalian cells. Pairs of defective herpes thymidine kinase (tk) sequences were introduced into mouse Ltk- cells on a DNA molecule that also contained a neo gene under control of the SV40 early promoter/enhancer. With the majority of the constructs used, gene conversions or double cross...

On the basis of their restriction endonuclease digestion patterns, four Australian bovine herpesvirus type 1 (BHV-1) isolates were classified as belonging to the BHV-1.2a subtypes. The thymidine kinase (TK) genes of all four BHV-1.2a isolates were located on a 3.5 kb SalI restriction fragment. This is in contrast to North American and European BHV-1.1 isolates whose TK genes are contained on a ...

The mechanism of posttranscriptional regulation of thymidine kinase (TK) enzyme levels following serum stimulation of quiescent cells has been investigated using stably transfected Rat 3 (TK1 cells containing the human TK complementary DNA linked to a hybrid SV4O/human TK promoter. These cells expressed a wild-type human TK mRNA at relatively constant levels during the first G1 and S phase afte...

Suicide gene therapy using herpes simplex virus-1 thymidine kinase (HSV-TK) in combination with ganciclovir (GCV) has emerged as a potential new method for treating cancer. We hypothesize that the efficacy of HSV-TK/GCV therapy is at least partially dependent on p53 status in hepatocellular carcinoma (HCC) patients. Using recombinant adenoviral vectors (rAdV), TK, p53, and ASPP2 were overexpres...