title: Cathepsin B mediates cleavage of herpes simplex virus type 1 origin binding protein (OBP) to yield OBPC-1, and cleavage is dependent upon viral DNA replication.
abstract: Although the seven viral proteins required for herpes simplex virus type 1 (HSV-1) DNA replication have been identified, the mechanism by which viral DNA synthesis is regulated is unclear. HSV-1 DNA replication is thought to occur in two stages: origin-dependent DNA replication (stage I) mediated by the origin binding protein (OBP), followed by origin- and OBP-independent DNA replication (stage II). The mechanism that facilitates the switch from stage I to stage II is unknown; however, it must involve the loss of OBP function or OBP itself from the replication initiation complex. Previous studies from this laboratory identified a transcript (UL8.5) and protein (OBPC) that are in frame with and comprise the C terminus of the gene specifying OBP. Because of its DNA binding ability, OBPC has been hypothesized to mediate the switch from stage I to stage II. Here, we identify a second protein (OBPC-2) that is also in frame with the C terminus of OBP but comprises a smaller portion of the protein. We demonstrate that the protein originally identified (OBPC-1) is a cathepsin B-mediated cleavage product of OBP, while OBPC-2 may be the product of the UL8.5 transcript. We further demonstrate that the cleavage of OBP to yield OBPC-1 is dependent upon viral DNA replication. These results suggest that cleavage may be a mechanism by which OBP levels and/or activity are regulated during infection.
authors.affiliation: Department of Medicine, Harvard Medical School at the Beth Israel Deaconess Medical Center, 330 Brookline Avenue, RN 123, Boston, MA 02215, USA.
authors.forename: Malen A
authors.initials: MA
authors.lastname: Link
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Silva
authors.forename: Priscilla A
authors.initials: PA
authors.lastname: Schaffer
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D008954:Models, Biological; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D014764:Viral Proteins; C064565:UL9 protein, Human herpesvirus 1; D002401:Cathepsin B