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Journal of Virology, September 2007, p. 9175-9182, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00676-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Malen A. Link, Laurie A. Silva, and Priscilla A. Schaffer*

Departments of Medicine and Microbiology and Molecular Genetics, Program in Virology, Harvard Medical School at Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215

Received 29 March 2007/ Accepted 30 May 2007

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.

* Corresponding author. Mailing address: Department of Medicine, Harvard Medical School at the Beth Israel Deaconess Medical Center, 330 Brookline Avenue, RN 123, Boston, MA 02215. Phone: (617) 667-2958. Fax: (617) 667-8540. E-mail: pschaffe{at}bidmc.harvard.edu

{triangledown} Published ahead of print on 6 June 2007.

Journal of Virology, September 2007, p. 9175-9182, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00676-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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