This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Isler, J. A.
Right arrow Articles by Schaffer, P. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Isler, J. A.
Right arrow Articles by Schaffer, P. A.

 Previous Article  |  Next Article 

Journal of Virology, January 2001, p. 628-637, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.628-637.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Phosphorylation of the Herpes Simplex Virus Type 1 Origin Binding Protein

Jennifer A. Isler and Priscilla A. Schaffer*

Department of Microbiology and Cell and Molecular Biology Graduate Group, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Received 31 July 2000/Accepted 26 October 2000

The herpes simplex virus type 1 (HSV-1) origin binding protein (OBP), the product of the UL9 gene, is one of seven HSV-encoded proteins required for viral DNA replication. OBP performs multiple functions characteristic of a DNA replication initiator protein, including origin-specific DNA binding and ATPase and helicase activities, as well as the ability to interact with viral and cellular proteins involved in DNA replication. Replication initiator proteins in other systems, including those of other DNA viruses, are known to be regulated by phosphorylation; however, the role of phosphorylation in OBP function has been difficult to assess due to the low level of OBP expression in HSV-infected cells. Using a metabolic labeling and immunoprecipitation approach, we obtained evidence that OBP is phosphorylated during HSV-1 infection. Kinetic analysis of metabolically labeled cells indicated that the levels of OBP expression and phosphorylation increased at approximately 4 h postinfection. Notably, when expressed from a transfected plasmid, a recombinant baculovirus, or a recombinant adenovirus (AdOBP), OBP was phosphorylated minimally, if at all. In contrast, superinfection of AdOBP-infected cells with an OBP-null mutant virus increased the level of OBP phosphorylation approximately threefold, suggesting that HSV-encoded viral or HSV-induced cellular factors enhance the level of OBP phosphorylation. Using HSV mutants inhibited at sequential stages of the viral life cycle, we demonstrated that this increase in OBP phosphorylation is dependent on early protein synthesis and is independent of viral DNA replication. Based on gel mobility shift assays, phosphorylation does not appear to affect the ability of OBP to bind to the HSV origins.

* Corresponding author. Mailing address: Beth Israel Deaconess Medical Center, Harvard University, 330 Brookline Ave., RN125, Boston, MA 02215. Phone: (617) 667-2958. Fax: (617) 667-7175. E-mail: pschaffe{at}caregroup.harvard.edu.

Journal of Virology, January 2001, p. 628-637, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.628-637.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Chattopadhyay, S., Weller, S. K. (2007). Direct Interaction between the N- and C-Terminal Portions of the Herpes Simplex Virus Type 1 Origin Binding Protein UL9 Implies the Formation of a Head-to-Tail Dimer. J. Virol. 81: 13659-13667 [Abstract] [Full Text]  
  • Link, M. A., Schaffer, P. A. (2007). 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. 81: 10699-10711 [Abstract] [Full Text]  
  • Link, M. A., Silva, L. A., Schaffer, P. A. (2007). 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. J. Virol. 81: 9175-9182 [Abstract] [Full Text]  
  • Chattopadhyay, S., Weller, S. K. (2006). DNA Binding Activity of the Herpes Simplex Virus Type 1 Origin Binding Protein, UL9, Can Be Modulated by Sequences in the N Terminus: Correlation between Transdominance and DNA Binding. J. Virol. 80: 4491-4500 [Abstract] [Full Text]  
  • Sariyer, I. K., Akan, I., Palermo, V., Gordon, J., Khalili, K., Safak, M. (2006). Phosphorylation Mutants of JC Virus Agnoprotein Are Unable To Sustain the Viral Infection Cycle.. J. Virol. 80: 3893-3903 [Abstract] [Full Text]  
  • Schildgen, O., Graper, S., Blumel, J., Matz, B. (2005). Genome Replication and Progeny Virion Production of Herpes Simplex Virus Type 1 Mutants with Temperature-Sensitive Lesions in the Origin-Binding Protein. J. Virol. 79: 7273-7278 [Abstract] [Full Text]  
  • Colletti, K. S., Xu, Y., Yamboliev, I., Pari, G. S. (2005). Human Cytomegalovirus UL84 Is a Phosphoprotein That Exhibits UTPase Activity and Is a Putative Member of the DExD/H Box Family of Proteins. J. Biol. Chem. 280: 11955-11960 [Abstract] [Full Text]  
  • Davido, D. J., von Zagorski, W. F., Lane, W. S., Schaffer, P. A. (2005). Phosphorylation Site Mutations Affect Herpes Simplex Virus Type 1 ICP0 Function. J. Virol. 79: 1232-1243 [Abstract] [Full Text]  
  • Marintcheva, B., Weller, S. K. (2003). Existence of Transdominant and Potentiating Mutants of UL9, the Herpes Simplex Virus Type 1 Origin-Binding Protein, Suggests that Levels of UL9 Protein May Be Regulated during Infection. J. Virol. 77: 9639-9651 [Abstract] [Full Text]  
  • Eom, C.-Y., Lehman, I. R. (2003). Replication-initiator protein (UL9) of the herpes simplex virus 1 binds NFB42 and is degraded via the ubiquitin-proteasome pathway. Proc. Natl. Acad. Sci. USA 100: 9803-9807 [Abstract] [Full Text]  
  • Advani, S. J., Weichselbaum, R. R., Roizman, B. (2001). cdc2 Cyclin-Dependent Kinase Binds and Phosphorylates Herpes Simplex Virus 1 UL42 DNA Synthesis Processivity Factor. J. Virol. 75: 10326-10333 [Abstract] [Full Text]  
  • Halford, W. P., Kemp, C. D., Isler, J. A., Davido, D. J., Schaffer, P. A. (2001). ICP0, ICP4, or VP16 Expressed from Adenovirus Vectors Induces Reactivation of Latent Herpes Simplex Virus Type 1 in Primary Cultures of Latently Infected Trigeminal Ganglion Cells. J. Virol. 75: 6143-6153 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»