CLONING AND SEQUENCE-ANALYSIS OF A MAREKS-DISEASE VIRUS ORIGIN-BINDING PROTEIN (OBP) REVEALS STRICT CONSERVATION OF STRUCTURAL MOTIFS AMONGOBPS OF DIVERGENT ALPHAHERPESVIRUSES

Marek's disease virus (MDV) is a highly cell-associated avian herpesvi rus. In its natural host, MDV induces Marek's disease (MD), a lethal c ondition characterized by malignant lymphoma of T cells. Although symp toms of MD may be prevented by vaccination, no practical pharmacologic al method of control has been widely accepted. Viral replication repre sents a point at which pharmacological control of herpesvirus infectio n may be most successful. However, this requires detailed knowledge of viral replication proteins. Studies in HSV-1 DNA replication implicat e the UL9 protein as a key initiator of replication. For example, bind ing of UL9 to HSV-1 origins is a prerequisite for assembly of addition al replication proteins. In this study, a protein, whose apparent mole cular size is similar to that of HSV-1 UL9, was identified in extracts of MDV infected cells by western blot analysis with anti-HSV-l UL9 an tibody. A putative MDV UL9 gene was subsequently identified through se quencing of MDV genome fragments (BamHI G and C). Extended DNA sequenc e analysis revealed an open reading frame (ORF) which could encode a p rotein homologous to HSV-I UL9. The MDV UL9 ORF encodes 841 amino acid s, producing a sequence 49% identical to HSV-1 UL9 and 46% identical t o VZV gene 51 product (VZV UL9). MDV UL9 shares numerous structural mo tifs with HSV-1 and VZV UL9 proteins, including six conserved N-termin al helicase motifs, an N-terminal leucine zipper motif, a C-terminal p seudo-leucine zipper sequence, and a putative helix-turn-helix structu re.