title: Cloning and sequence analysis of a Marek's disease virus origin binding protein (OBP) reveals strict conservation of structural motifs among OBPs of divergent alphaherpesviruses.
abstract: Marek's disease virus (MDV) is a highly cell-associated avian herpesvirus. In its natural host, MDV induces Marek's disease (MD), a lethal condition characterized by malignant lymphoma of T cells. Although symptoms of MD may be prevented by vaccination, no practical pharmacological method of control has been widely accepted. Viral replication represents a point at which pharmacological control of herpesvirus infection may be most successful. However, this requires detailed knowledge of viral replication proteins. Studies in HSV-1 DNA replication implicate the UL9 protein as a key initiator of replication. For example, binding of UL9 to HSV-1 origins is a prerequisite for assembly of additional replication proteins. In this study, a protein, whose apparent molecular size is similar to that of HSV-1 UL9, was identified in extracts of MDV infected cells by western blot analysis with anti-HSV-1 UL9 antibody. A putative MDV UL9 gene was subsequently identified through sequencing of MDV genome fragments (BamHI G and C). Extended DNA sequence analysis revealed an open reading frame (ORF) which could encode a protein homologous to HSV-1 UL9. The MDV UL9 ORF encodes 841 amino acids, producing a sequence 49% identical to HSV-1 UL9 and 46% identical to VZV gene 51 product (VZV UL9). MDV UL9 shares numerous structural motifs with HSV-1 and VZV UL9 proteins, including six conserved N-terminal helicase motifs, an N-terminal leucine zipper motif, a C-terminal pseudo-leucine zipper sequence, and a putative helix-turn-helix structure.
authors.affiliation: Department of Microbiology, Michigan State University, East Lansing 48824, USA.
authors.forename: T F
authors.initials: TF
authors.lastname: Wu
authors.forename: W
authors.initials: W
authors.lastname: Sun
authors.forename: M
authors.initials: M
authors.lastname: Boussaha
authors.forename: R
authors.initials: R
authors.lastname: Southwick
authors.forename: P M
authors.initials: PM
authors.lastname: Coussens
mesh_terms: D018138:Alphaherpesvirinae; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D003001:Cloning, Molecular; D004279:DNA, Viral; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D008381:Herpesvirus 2, Gallid / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D018741:Replication Origin; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; D014764:Viral Proteins; C055789:origin-binding proteins, viral; C064565:UL9 protein, Human herpesvirus 1