Disease relevance of UL30

• They showed a high homology with alphaherpesvirus homologs despite large differences in the G + C content of the UL30-UL28 segment ranging from 44.4% for varicella zoster virus to 71.5% for BHV-1 [1].
• The mode of action of 2'NDG appears to involve phosphorylation by herpes simplex virus thymidine kinase and subsequent phosphorylations by cellular kinases to produce 2'NDG triphosphate, which is a potent inhibitor of herpes virus DNA polymerase [2].
• The Km/Ki ratio for DNA polymerase alpha was 47, as compared with 4.6 for HSV-1 DNA polymerase [3].
• This sequence showed a high percentage of identity with the DNA polymerase genes of herpesviruses of the oncogenic subfamily Gammaherpesvirinae [4].
• Using phosphonoacetic acid to prevent virus DNA synthesis by inhibition of the BHV-1 DNA polymerase, 28 early transcripts were recognized [5].

High impact information on UL30

• Trisodium phosphonoformate selectively inhibits cell-free DNA polymerase activity induced by herpesvirus [6].
• Common therapies for herpes viral infections employ nucleoside analogs, such as Acyclovir, and target the viral DNA polymerase, essential for viral DNA replication [7].
• The viral DNA polymerase binds strongly to the acyclo-GMP-terminated template, and in thereby inactivated [8].
• Drug resistance to compound 14 correlated to point mutations in conserved domain III of the herpesvirus DNA polymerase, but these mutations do not confer resistance to existing nucleoside therapy [9].
• It has high, selective activity against varicella zoster virus (VZV), inhibiting VZV replication, possibly through competitive inhibition of viral DNA polymerase, or by acting as an alternative substrate to deoxythymidine triphosphate, causing viral DNA strand breakage [10].

Biological context of UL30

• We used a novel type of primer system, a system that uses stair primers, in which the primer sequences are based on consensus sequences in the DNA polymerase gene of herpesvirus to detect herpesviruses by PCR [11].
• In this study, gene expression of SVV open reading frames (ORFs) 28 and 29, which encode the viral DNA polymerase and DNA-binding protein, respectively, was characterized during lytic infection of Vero cells [12].

Anatomical context of UL30

• Initially, samples of peripheral blood mononuclear cells (PBMC), spleens, lungs, kidneys and livers of pigs from Germany and Spain were tested with a PCR assay which targets conserved regions of the herpesvirus DNA polymerase gene with degenerate and deoxyinosine-substituted primers [4].
• Disruption of focal contact points was seen early after infection and was prevented by an inhibitor of viral DNA polymerase, phosphonoacetic acid [13].
• METHODS: Twenty-one intraocular fluids collected from 19 patients were subjected to cultures for HSV and uniplex PCR (uPCR) for DNA polymerase gene [14].

Associations of UL30 with chemical compounds

• The mechanism of potentiation was found to reside in the depletion of endogenous dGTP pools, which favored the inhibitory effect of the triphosphate of ACV, GCV, or PCV on the viral DNA polymerase [15].
• Moreover, the only classes of compounds licensed for systemic treatment of disease are nucleoside, nucleotide and pyrophosphate analogues; all of these ultimately target the herpesvirus DNA polymerase [16].
• The viral DNA was nick translated in the presence of biotin-dUTP with DNA polymerase to incorporate biotin into the newly synthesized strand [17].
• Currently available second line agents for the treatment of herpesvirus infections--the pyrophosphate analogue foscarnet and the acyclic nucleoside phosphonate derivative cidofovir--also inhibit the viral DNA polymerase but are not dependent on prior viral-specific activation [18].

Other interactions of UL30

• 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 UL30

• Degenerate PCR primers which amplify a conserved region of the DNA polymerase genes of the herpesvirus family were used to provide sequence evidence for a new bovine herpesvirus in bovine B-lymphoma cells and peripheral blood mononuclear cells (PBMC) [20].
• This virus-induced DNA polymerase was partially purified and separated from host cell enzymes by DEAE-cellulose and phosphocellulose column chromatographies [21].

References