Disease relevance of UL2

• Herpes simplex virus (HSV) encodes a uracil DNA glycosylase (UNG; UL2), which has been shown to be dispensable for normal replication of HSV-1 in cultured cells (J. Mullaney, H.W. Moss, and D.J. McGeoch, J. Gen. Virol. 70:449-454, 1989) [1].
• The UL2 open reading frame, present within both the EHV-1 standard and DIP genomes, was inserted into the transcription expression vector pGEM-3Z to yield constructs pGEML2 and pDIL2, respectively [2].
• Polyclonal antiserum was raised against the UL2 protein by injecting rabbits with a TrpE/UL2 fusion protein expressed from plasmid pATH23L2 in Escherichia coli [2].
• Transcriptional and translational analyses of the UL2 gene of equine herpesvirus 1: a homolog of UL55 of herpes simplex virus type 1 that is maintained in the genome of defective interfering particles [2].
• DNA sequences at the L terminus, which contain the UL2 gene (homolog of UL55 of herpes simplex virus type 1 and open reading frame 3 of varicella-zoster virus) of standard EHV-1, have been shown to be highly conserved in all clones of the EHV-1 DIP genome [2].

High impact information on UL2

• The Bacillus subtilis bacteriophages PBS-1 and PBS-2 protect their uracil-containing DNA by expressing an inhibitor protein (UGI) which inactivates the host uracil-DNA glycosylase (UDGase) base-excision repair enzyme [3].
• Evidence that the herpes simplex virus type 1 uracil DNA glycosylase is required for efficient viral replication and latency in the murine nervous system [1].
• The UL2 mRNA was characterized by S1 nuclease analyses, which mapped the 5' and 3' termini of the 0.9-kb early UL2 mRNA to approximately 26 and 16 nucleotides downstream of a TTTAAA box and polyadenylation signal, respectively [2].
• Herpes simplex virus type 1 uracil-DNA glycosylase: isolation and selective inhibition by novel uracil derivatives [4].
• Short-term [3H]thymidine incorporation into the DNA of HeLa cells in culture was partially inhibited by OctAU, whereas it was unchanged when 6-(p-n-hexylanilino)uracil was present at concentrations that completely inhibited HSV1 uracil-DNA glycosylase activity [4].

Biological context of UL2

• A 28.5 kDa catalytic fragment of the uracil-DNA glycosylase DNA repair enzyme from Herpes simplex virus type 1 (HSV-1) has been crystallized using protein from a highly expressing Escherichia coli clone of the Herpes simplex virus type 1 UL2 gene [5].
• Viral mutants with lesions in either or both of genes UL2 and UL44, which are not essential for growth in cell culture, were constructed using cosmids containing specifically introduced frameshift mutations [6].
• Hence, HSV1 uracil-DNA glycosylase, dispensable in viral proliferation in tissue culture, could be essential in neurons for the "cleansing" of the viral genome of uracil residues before the start of replication [7].
• We conclude that the damage recognition step in the HSV-1 UDG reaction pathway is modulated by local DNA sequence [8].
• Systematic examination of the kinetics and binding of UDG with these different substrates has enabled us to examine the origin of the sequence preferences [8].

Anatomical context of UL2

• The results suggest their possible use to evaluate the functional role of HSV1 uracil-DNA glycosylase in viral infections and re-activation in nerve cells [4].

Analytical, diagnostic and therapeutic context of UL2

• The UL2-specific antiserum reacted in Western immunoblot and immunoprecipitation analyses with a 23-kDa polypeptide synthesized in cells infected with standard EHV-1 or DIP-enriched virus [2].
• Site-directed mutants of the herpes simplex virus type 1 uracil-DNA glycosylase lacking catalytic activity have been used to probe the substrate recognition of this highly conserved and ubiquitous class of DNA-repair enzyme utilizing surface plasmon resonance [9].

References