Disease relevance of UL23

• We also report that, in mice and rabbits in vivo, the compound is effective against both local and systemic infections with herpes simplex virus type 1, including herpetic keratitis caused by a TK- mutant which is resistant to the classical anti-herpes drugs [1].
• Chicken ovalbumin gene fused to a herpes simplex virus alpha promoter and linked to a thymidine kinase gene is regulated like a viral gene [2].
• The cellular localization of the precore/core and core proteins was studied by immunofluorescence following transfection of 143 thymidine kinase-negative (TK ) and Hep-G2 cells with expression constructs containing wild-type (hepatitis B e antigen [HBeAg]-positive) and precore mutant (HBeAg-negative) sequences [3].
• For suicide gene therapy, VP22 activity was demonstrated under hypoxia by coupling VP22 to the HSV thymidine kinase (HSVtk) [4].
• (iii) HSV-1(HFEM)tsB7 induced the alpha-TK gene chimeras at the nonpermissive (39 degrees C) temperature; at 39 degrees C the parental HSV-1(HFEM)tsB7 capsids accumulate at nuclear pores and do not release viral DNA [5].

High impact information on UL23

• The therapeutic effect is achieved by the selective killing of thymidine kinase gene-modified activated T cells by ganciclovir (GCV) [6].
• Here, we aimed to determine whether an immunopathological process induced by a viral infection could be controlled by GCV when T cells express a thymidine kinase transgene [6].
• From this, we conclude that proteins that bind TK and facilitate its cytoplasmic accumulation do not travel through a CRM1-dependent RNA transport pathway [7].
• Multiple cis-acting RNA sequences, or subelements, that induce cytoplasmic localization of unspliced RNA were mapped within the TK gene [7].
• Furthermore, like HBV PRE-containing RNA, TK cytoplasmic localization is not sensitive to leptomycin B, a drug that inhibits the export of proteins containing nuclear export signals [7].

Chemical compound and disease context of UL23

• Moreover, two of the most potent TK-2 inhibitors (18 and 26b) that also inhibit HSV-1 TK were able to reverse the cytostatic activity of 1-(beta-D-arabinofuranosyl)thymine (Ara-T) and ganciclovir in HSV-1 TK-expressing OST-TK-/HSV-1 TK+ cell cultures [8].
• Thymidine kinase mutations conferring acyclovir resistance in herpes simplex type 1 recombinant viruses [9].
• Novel N1-substituted thymine derivatives related to 1-[(Z)-4-(triphenylmethoxy)-2-butenyl]thymine have been synthesized and evaluated against thymidine kinase-2 (TK-2) and related nucleoside kinases [i.e., Drosophila melanogaster deoxynucleoside kinase (Dm-dNK) and herpes simplex virus type 1 thymidine kinase (HSV-1 TK)] [8].
• Reactivation of acyclovir-resistant thymidine kinase-deficient herpes simplex virus harbouring single base insertion within a 7 Gs homopolymer repeat of the thymidine kinase gene [10].

Biological context of UL23

• Cloned HSV DNA fragments derived from various parts of the genome were cotransfected into BHK cells together with chimaeric plasmids which contained the thymidine kinase gene under IE control [11].
• This enhancer potentiates a marked increased activity from the heterologous thymidine kinase promoter in an orientation-independent manner and at a proximal, as well as a distal, location [12].
• (Cell 24:555-565, 1981) have shown that chimeric genes constructed by fusion of 5' noncoding leader and upstream sequences of alpha genes to the 5' noncoding leader and structural sequences of the viral thymidine kinase (TK), a beta gene, are regulated as alpha genes upon recombination into the viral genome [5].
• We identified cis-acting elements in the intronless herpes simplex virus type 1 thymidine kinase (TK) gene that facilitate intron-independent gene expression [7].
• In cells converted from TK- to TK+ phenotype, these chimeric genes are induced by infection with homologous TK- virus [5].

Associations of UL23 with chemical compounds

• Compound 26b competitively inhibited TK-2 with respect to thymidine and uncompetitively with respect to ATP [8].
• N1-substituted thymine derivatives as mitochondrial thymidine kinase (TK-2) inhibitors [8].
• Compounds with a hexamethylene spacer (18, 26b, 31) displayed the highest inhibitory values against TK-2 (IC50 = 0.3-0.5 microM) [8].
• RESULTS: The acyclovir-resistant virus, with a Thr63Ile change in the ATP-binding site of the thymidine kinase gene, produced almost as many skin lesions as the wild-type susceptible virus [13].
• This differs from the results for CV where only idoxuridine and bromodeoxyuridine appeared to be activated, putatively by the type II TK expressed by this virus [14].

Analytical, diagnostic and therapeutic context of UL23

• (iv) The alpha-TK gene chimeras were not induced by infection with spontaneous TK- mutants of pseudorabies virus and bovine mammillitis virus or with human cytomegalovirus or adenovirus type 2 or by exposure to lysates of HSV-1-infected cells from which the virus was removed by centrifugation [5].
• We used a variety of techniques, including two-color flow cytometry and cytotoxicity assays to detect the presence of TK in the non-producing cells [15].

References