Disease relevance of UL5

• Herpes simplex virus 1 encodes a helicase-primase that is composed of the products of the UL5, UL8, and UL52 genes [1].
• Herpes simplex virus type 1 (HSV-1) encodes a heterotrimeric helicase-primase comprised of the products of the UL5, UL8, and UL52 genes (Crute, J. J., and Lehman, I. R. (1991) J. Biol. Chem. 266, 4484-4488) [2].
• To provide conclusive evidence that UL5 is the only HSV-2 gene involved in the restricted replication phenotype of R13-1, we have characterized the phenotype of a recombinant virus (IB1) in which only the UL5 gene of HSV-1 was replaced by HSV-2 UL5 [3].
• The UL5 gene product was overexpressed in Escherichia coli and used to generate polyclonal antibodies which detected proteins in HSV-1-infected cell extracts from 4 hr postinfection [4].
• Characterisation of IE and UL5 gene products of equine herpesvirus 1 using DNA inoculation of mice [5].

High impact information on UL5

• The defect was localized to the UL5 open reading frame by using marker rescue analysis (D. C. Bloom and J. G. Stevens, J. Virol. 68:3761-3772, 1994) [3].
• Marker rescue analysis localized the fragment responsible for restoring neurovirulence to UL5, a component of the origin-binding complex implicated in replication of the viral genome [6].
• A transient replication complementation assay was used to test the effect of each mutation on the function of the UL5 protein in viral DNA replication [7].
• In this assay, a mutant UL5 protein expressed from an expression clone is used to complement a replication-deficient null mutant with a mutation in the UL5 gene for the amplification of herpes simplex virus origin-containing plasmids [7].
• In this study, we isolated a permissive cell line (L2-5) which contains the wild-type UL5 gene under the control of the strong and inducible promoter for the large subunit of herpes simplex virus type 1 ribonucleotide reductase (ICP6) [8].

Biological context of UL5

• Immunochemical analysis has shown these polypeptides to be the products of three of the genes UL52, UL5, and UL8 that are required for replication of a plasmid containing a herpes simplex 1 origin (oriS) [9].
• In this study, we have examined the functional significance of these six motifs for the UL5 protein through the introduction of site-specific mutations resulting in single amino acid substitutions of the most highly conserved residues within each motif [7].
• Sequence analysis of the UL5 gene predicts that the 99-kDa protein contains a consensus sequence for an ATP binding site [4].

Other interactions of UL5

• Sequence analysis of the HSV-1 genome has revealed the existence of two open reading frames, UL5 and UL6, within this fragment (D. McGeoch, M. Dalrymple, A. Dolan, D. McNab, L. Perry, P. Taylor, and M. Challberg, 1988, J. Virol. 62, 444-453) [4].

Analytical, diagnostic and therapeutic context of UL5

• In this paper we report fine mapping and sequence analysis of the mutations in tsK13 and tsM19 which unambiguously localize the mutations to UL5, predicted to encode a 99-kDa polypeptide [4].
• Indirect immunofluorescence staining revealed that the UL5 gene product localizes to the nucleus in two patterns: diffuse staining throughout the nucleus and in discrete globules which appear at the periphery of the nucleus [4].
• Western blotting on EHV-1 infected RK13 cells showed multiple IE products of 120-200 kDa and a UL5 product of 52 kDa [5].
• Helicase inhibitors that target the HSV helicase-primase complex comprised of the UL5, UL8 and UL52 proteins have recently been shown to effectively control HSV infection in animal models [10].

References