Disease relevance of UL23

• The thymidine kinase gene of herpes simplex virus 1 was mutated by inserting oligodeoxynucleotide linkers into the region of the gene corresponding to the 5' untranslated portion of the mRNA [1].
• One of the cell lines is able to complement the functional defect found in two temperature-sensitive mutants of HSV 1, and reversion of the cells to a thymidine kinase-negative phenotype results in the loss of this capability [2].
• Formation of infectious progeny virus after insertion of herpes simplex thymidine kinase gene into DNA of an avian retrovirus [3].
• Introduction of the herpes simplex virus thymidine kinase gene into mouse cells using virus DNA or transformed cell DNA [2].
• In converted tk+ cells, the fused thymidine kinase gene, like the wild-type gene, is stimulated by superinfection with the tk- virus [4].

Psychiatry related information on UL23

• Inhibition of herpes simplex virus (HSV) thymidine kinase (TK) gene transcription (pHSV-106, pML-BPV-TK4) by DNA methylation is an indirect effect, which occurs with a latency period of approximately equal to 8 hr after microinjection of the DNA into TK- rat 2 and mouse LTK- cells [5].
• Using the highly sensitive polymerase chain reaction, we have detected the viral thymidine kinase gene in post-mortem brain from 14/21 cases of senile dementia of the Alzheimer type and 9/15 elderly normals [6].

High impact information on UL23

• This report describes studies on the kinetics of herpes thymidine kinase (TK) mRNA transport in X. laevis oocytes as studied by microinjection and microdissection [7].
• We show that TK mRNA nuclear transport in this cell can be dramatically altered by introduction of specific DNA sequences into the nucleus [7].
• We constructed mutated a sequences, inserted them into the thymidine kinase gene, and recombined them into the L component of the viral genome [8].
• We have characterized an in vitro transcription system derived from uninfected HeLa cells that accurately initiates RNA synthesis at the herpes virus thymidine kinase (TK) promoter [9].
• DNAase I footprint experiments with wild-type and mutant promoters reveal that the TK upstream elements contain three distinctive protein binding sites, two of which appear to be recognized by the Sp1 transcription factor and one which interacts with a cellular protein that binds to "CCAAT" sequences [9].

Chemical compound and disease context of UL23

• Altered substrate specificity of herpes simplex virus thymidine kinase confers acyclovir-resistance [10].
• Mouse cells transformed with herpes simplex virus and containing the viral thymidine kinase (TK) gene in an inactive state were treated with 5-azacytidine [11].
• Hybrids were exposed to bromodeoxyuridine (BrdUrd) as a means of selection for cells that had lost HSV-2 TK activity [12].
• The herpes simplex virus type-2 (HSV-2)-transformed human cell line HB-2-3 was fused with thymidine kinase (TK)-deficient mouse cells [LM(TK-)], and 12 independent hybrids were isolated with the use of the HAT (hypoxanthine, amethopterin, and thymidine)-ouabain selection system [12].
• Extensive vitiligo after ganciclovir treatment of GvHD in a patient who had received donor T cells expressing herpes simplex virus thymidine kinase [13].

Biological context of UL23

• To examine this phenomenon further, a plasmid containing HSV thymidine kinase and human alpha- and gamma-globin genes was transfected into mouse L cells [14].
• Mouse L cells lacking the enzyme thymidine kinase (LMTK-) have been converted to a TK+ phenotype by infection with fragmented HSV2 strain 333 DNA [15].
• The acquired phenotype was demonstrated to be donor-derived by analysis of the electrophoretic mobility of the tk activity, and the presence of HSV DNA sequences in the recipient cells was demonstrated [16].
• In the first step of the procedure, the herpes simplex virus thymidine kinase is inserted into the genome at a specific site [17].
• Transfection experiments with HSV 1 in which one uses herpes simplex virus (HSV) thymidine kinase (TK) as a selectable prototrophic marker yield two classes of transformed cells: stable and unstable [18].

Anatomical context of UL23

• When DNA was delivered directly into the nuclei of LMTK-, a mouse cell line deficient in thymidine kinase activity, 50--100% of the cells expressed TK enzymatic activity [19].
• We examined the molecular basis of modulation of transfected herpes simplex virus (HSV) thymidine kinase (tk) gene in mouse fibroblasts [20].
• The recombinant virus carrying the thymidine kinase inserted into the gene 22 and viruses exhibiting 0.1 kb and 0.7 kb deletions in the gene 22 specify new alpha polypeptides with molecular weights approximately 30% of the wild-type gene 22 product and grown normally in Vero cell cultures [17].
• In companion experiments, we used high molecular weight DNA derived from tissues and cultured cells of a variety of species to transfer tk activity [16].
• A plasmid, designated pMK, containing the structural gene for thymidine kinase from herpes simplex virus (HSV) fused to the promoter/regulatory region of the mouse metallothionein-I gene, was injected into the pronucleus of fertilized one-cell mouse eggs; the eggs were subsequently reimplanted into the oviducts of pseudopregnant mice [21].

Associations of UL23 with chemical compounds

• Two virus-coded enzymes are important in the mechanism of action of this drug: thymidine kinase (TK) which initiates its activation by converting it to the monophosphate and DNA polymerase whose action is inhibited by ACV triphosphate [10].
• The induction of TK expression by 5-azacytidine was concentration-dependent, with maximal induction at 10 micromoles per liter [11].
• Investigation into the mechanism of the acyclovir resistance revealed changes in the thymidine-kinase activity of both isolates [22].
• Transfections of the cisplatin-sensitive cells resulted in no sensitization to ganciclovir with pMT-TK (IC(50) 200 microg/mL) and a high sensitization with pCD3-TK (IC(50) = 6 microg/mL) [23].
• Discontinuous polyacrylamide gel electrophoresis studies demonstrated that the HSV-2-specific TK was the selected enzyme in the hybrids [12].

Regulatory relationships of UL23

• We infer that UL24 is expressed and important for virus growth in cell culture and suggest that possible effects on UL24 should be considered in studies of thymidine kinase-deficient mutants [24].

Other interactions of UL23

• In cells producing defective virus, there was thymidine kinase activity, but the viral deoxyribonuclease activity was considerably reduced [25].

Analytical, diagnostic and therapeutic context of UL23

• Furthermore, autoradiography of the cells still expressing TK shows that 3H-thymidine incorporation is reduced [26].
• Direct microinjection of DNA by glass micropipettes was used to introduce the Herpes simplex virus thymidine kinase gene into cultured mammalian cells [19].
• The tk+ mouse cells transformed with human DNA were shown to express human type tk activity as determined by isoelectric focusing [16].
• Southern blot analyses demonstrated that functional thymidine kinase genes were generated by homologous recombination between the two deletion mutants [27].
• CONCLUSION: These studies suggest that pMT-TK gene therapy may provide an alternative treatment for cisplatin-refractory ovarian tumors [23].

References