Disease relevance of UL23

• Sequence and transcript analysis of the bovine herpesvirus 1 thymidine kinase locus [1].
• 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 [2].
• (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 [3].
• (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 [3].
• Compound 7 exhibits potent and selective activity against thymidine kinase encoding herpesviruses, in particular, HSV-1 and HSV-2 [4].

High impact information on UL23

• By reverse transcription (RT)-PCR, IE (bICP4), E (thymidine kinase, ribonucleotide reductase [RR]), L (glycoprotein C, and alpha trans-inducing factor), and dual-kinetic (bICP0 and bICP22) transcripts were analyzed [5].
• A thymidine kinase-negative bovine cell line isolated in our laboratory was used in these studies [6].
• Bovine herpesvirus 1 has been reported to contain a thymidine kinase (tk) gene which is nonessential for virus replication [6].
• (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 [3].
• In cells converted from TK- to TK+ phenotype, these chimeric genes are induced by infection with homologous TK- virus [3].

Chemical compound and disease context of UL23

• A detailed sequence and transcript analysis of the thymidine kinase (tk) gene of bovine herpesvirus 1 (BHV1, Cooper strain) was carried out [1].
• (E)-5-(2-Bromovinyl)-2'-deoxyuridine (BVdU) was phosphorylated by the bovine herpesvirus 1 (BHV-1)-induced thymidine kinase and subsequently incorporated into viral DNA, resulting in DNA that was more dense than DNA from untreated cells [7].

Biological context of UL23

• A tk open reading frame (ORF) of 1077 bp was identified and compared with tk ORFs previously published for other strains of BHV1 [1].
• An open reading frame (ORF) of 293 codons which partially overlaps the bovine herpesvirus 1 (BHV1) thymidine kinase (tk) ORF in a head-to-head orientation has been identified by nucleotide sequence analysis [8].
• The phosphorylation of BVdU was a prerequisite for its effect on glycosylation since the glycoproteins of a thymidine kinase-deficient mutant of BHV-1 were not affected [7].
• Since the thymidine kinase (TK) activity of herpesviruses has been associated with virulence, inactivation of the encoding gene in the ILTV genome should attenuate the virus [9].
• Alignment of the predicted amino acid sequence of the BHV-1 TK polypeptide with different herpesvirus TKs revealed five strongly conserved regions and also identified putative functional relationships with other enzymes [10].

Anatomical context of UL23

• The genetic experiments entailed the isolation of a bromodeoxyuridine (BrdUrd)-resistant rabbit cell line [RAB(BU)] deficient in cytosol TK activity and of BrdUrd- and araT-resistant BHV-1 mutants [11].
• Cytosol thymidine kinase (TK) activity is enhanced at 6 hr after bovine embryo tracheal (EBTr) and rabbit skin fibroblast (RAB-9) cells are infected with the Los Angeles and Cooper strains of bovine herpesvirus type 1 (BHV-1) [11].
• Virus was isolated from 3 fetuses, and all isolates were TK+ virus [12].
• Likewise, tk- BHV-1 was isolated from the buffy coat fraction of IV vaccinated calves, but not from nasal swabs. tk- BHV-1 vaccination reduced the multiplication of tk+ BHV-1 in the nasal mucosa, but did not completely prevent development of a persistent infection by the challenge virus [13].
• The PCR amplification used primers targeting the BHV-1 thymidine kinase gene and a nucleic acid releasing cocktail (GeneReleaser); the PCR product was used as the DNA probe in dot blot hybridization; virus isolation was done in primary bovine fetal testis (BFT) cell cultures [14].

Associations of UL23 with chemical compounds

• Except for five single base substitutions, our results indicate that the Cooper, Q3932, and LA strains share the same tk sequence [1].
• Northern blot analysis indicated that the tk transcript was 3' coterminal with the downstream 3.1-kb transcript which encodes a BHV1 homologue of the HSV1 H glycoprotein (gH) [1].
• The tk gene sequence of mutant B2 revealed the deletion of three bases resulting in the loss of valine at amino acid residue 174 of the TK polypeptide [10].
• During infection of cells without metabolic inhibitors these transcripts were detected as early as 2 hr postinfection (p.i.) and accumulated to 8 hr p.i. The early gene probe, thymidine kinase, hybridized with a 4.3-kb RNA that was detected in the presence of phosphonoacetic acid (PAA), but not in the presence of CH [15].
• The BHV-1 TK PCR using GeneReleaserTM has a detection limit of 1 picogram and 10 fentograms of purified BHV-1 DNA using ethidium bromide stained gel and Southern blot hybridization, respectively [16].

Other interactions of UL23

• The BHV1 UL24-like ORF is contained within a 5.2-kb RNA transcript initiating within the tk ORF and is the largest in a group of four 3'-coterminal transcripts [8].
• Induced cell lines transactivated the native BICP0 promoter as well as the herpes simplex virus thymidine kinase promoter and the long terminal repeat sequences of human immunodeficiency virus in a dose dependent manner [17].
• Virulence and immunogenicity in calves of thymidine kinase- and glycoprotein E-negative bovine herpesvirus 1 mutants [18].
• Hybridization analysis using BHV1.1 cloned probes of the immediate-early protein gene, thymidine kinase gene, DNA binding/DNA polymerase gene, and glycoprotein III gene provided information for mapping of these genes to the BHV5 encephalitic isolate [19].

Analytical, diagnostic and therapeutic context of UL23

• The size of the tk mRNA was determined by Northern blot analysis [1].
• Intramuscular and intravaginal vaccination of pregnant cows with thymidine kinase-negative, temperature-resistant infectious bovine rhinotracheitis virus (bovine herpes virus 1) [20].
• Establishment of conditions for the detection of bovine herpesvirus-1 by polymerase chain reaction using primers in the thymidine kinase region [16].

References