Herpes Simplex Virus Type 1 C-terminal Variants of the Origin Binding Protein (Obp), Obpc-1 and Obpc-2, Cooperatively Regulate Viral Dna Levels in Vitro, and Obpc-2 Affects Mortality in Mice.
From: Department of Medicine, Harvard Medical School at Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Journal of virology
- Publish Date: Oct 2007
- ISSN: 0022-538X
- Volume: 81
- Issue: 19
- Pages: 10699-711
- Medium: Print
- Language: English
- Citation (JAMA): Link Malen A, Schaffer Priscilla A, et al. Herpes Simplex Virus Type 1 C-terminal Variants of the Origin Binding Protein (Obp), Obpc-1 and Obpc-2, Cooperatively Regulate Viral Dna Levels in Vitro, and Obpc-2 Affects Mortality in Mice.. J. Virol. Oct 2007;81:10699-711
Abstract
Two in-frame, C-terminal isoforms of the herpes simplex virus type 1 (HSV-1) origin binding protein (OBP), OBPC-1 and OBPC-2, and a unique C-terminal transcript, UL8.5, are specified by HSV-1 DNA. As the first isoform identified, OBPC-1 was initially assumed to be the product of the UL8.5 transcript. Recent evidence has demonstrated, however, that OBPC-1 is a cathepsin B-mediated cleavage product of OBP, suggesting that OBPC-2 is the product of the UL8.5 transcript. Because both OBPC-1 and -2 contain the majority of the OBP DNA binding domain, we hypothesized that both may be involved in regulating origin-dependent, OBP-mediated viral DNA replication. In this paper, we demonstrate that OBPC-2 is, indeed, the product of the UL8.5 transcript. The translational start site of OBPC-2 was mapped, and a virus (M571A) that does not express this protein efficiently was constructed. Using M571A, we have shown that OBPC-2 is able to bind origin DNA, even though it lacks seven N-terminal amino acid residues of the previously mapped OBP DNA binding domain, resulting in a revision of the limits of the OBP DNA binding domain. Consistent with their proposed roles in regulating viral DNA replication, OBPC-1 and -2 act together to down-regulate viral DNA replication in vitro. During functional studies in vivo, OBPC-2 was identified as a factor that increases mortality in the mouse ocular model of HSV-1 infection.
Mesh Headings (Keywords): Animals, DNA Replication, DNA, Viral, Herpes Simplex, Herpesvirus 1, Human, Mice, Mutation, Origin Recognition Complex, Protein Biosynthesis, Protein Isoforms, Protein Structure, Tertiary, Replication Origin, Transcription, Genetic, Virus Latency, Virus Replication
Check for Full Text / PubMed Unique Identifier (PMID): 17634223
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