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 Asai, R.
Right arrow Articles by Kawaguchi, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Asai, R.
Right arrow Articles by Kawaguchi, Y.

 Previous Article  |  Next Article 

Journal of Virology, June 2006, p. 5125-5134, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02674-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Epstein-Barr Virus Protein Kinase BGLF4 Is a Virion Tegument Protein That Dissociates from Virions in a Phosphorylation-Dependent Process and Phosphorylates the Viral Immediate-Early Protein BZLF1

Risa Asai,1,3 Ai Kato,3 Kentaro Kato,4,{dagger} Mikiko Kanamori-Koyama,3,4,{ddagger} Ken Sugimoto,1,3 Takeshi Sairenji,5 Yukihiro Nishiyama,3 and Yasushi Kawaguchi1,2,3,4*

Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639,1 PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012,2 Department of Virology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550,3 Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510,4 Division of Biosignaling, Department of Biomedical Science, School of Life Science, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan5

Received 21 December 2005/ Accepted 14 March 2006

Epstein-Barr virus (EBV) BGLF4 is a viral protein kinase that is expressed in the lytic phase of infection and is packaged in virions. We report here that BGLF4 is a tegument protein that dissociates from the virion in a phosphorylation-dependent process. We also present evidence that BGLF4 interacts with and phosphorylates BZLF1, a key viral regulator of lytic infection. These conclusions are based on the following observations. (i) In in vitro tegument release assays, a significant fraction of BGLF4 was released from virions in the presence of physiological NaCl concentrations. (ii) Addition of physiological concentrations of ATP and MgCl2 to virions enhanced BGLF4 release, but phosphatase treatment of virions significantly reduced BGLF4 release. (iii) A recombinant protein containing a domain of BZLF1 was specifically phosphorylated by purified recombinant BGLF4 in vitro, and BGLF4 altered BZLF1 posttranslational modification in vivo. (iv) BZLF1 was specifically coimmunoprecipitated with BGLF4 in 12-O-tetradecanoylphorbol-13-acetate-treated B95-8 cells and in COS-1 cells transiently expressing both of these viral proteins. (v) BGLF4 and BZLF1 were colocalized in intranuclear globular structures, resembling the viral replication compartment, in Akata cells treated with anti-human immunoglobulin G. Our results suggest that BGLF4 functions not only in lytically infected cells by phosphorylating viral and cellular targets but also immediately after viral penetration like other herpesvirus tegument proteins.

* Corresponding author. Mailing address: Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81-3-6409-2070. Fax: 81-3-6409-2072. E-mail: ykawagu{at}ims.u-tokyo.ac.jp.

{dagger} Present address: Department of Veterinary Microbiology, Graduate School of Agricultural and Life Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

{ddagger} Present address: Global Drug Discovery, Discovery Research Laboratories, Shionogi & Co. Ltd., 2-5-1, Settsu-shi, Mishima, Osaka 566-0022, Japan.

Journal of Virology, June 2006, p. 5125-5134, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02674-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wang, F.-Z., Roy, D., Gershburg, E., Whitehurst, C. B., Dittmer, D. P., Pagano, J. S. (2009). Maribavir Inhibits Epstein-Barr Virus Transcription in Addition to Viral DNA Replication. J. Virol. 83: 12108-12117 [Abstract] [Full Text]  
  • Bailey, S. G., Verrall, E., Schelcher, C., Rhie, A., Doherty, A. J., Sinclair, A. J. (2009). Functional Interaction between Epstein-Barr Virus Replication Protein Zta and Host DNA Damage Response Protein 53BP1. J. Virol. 83: 11116-11122 [Abstract] [Full Text]  
  • Feederle, R., Mehl-Lautscham, A. M., Bannert, H., Delecluse, H.-J. (2009). The Epstein-Barr Virus Protein Kinase BGLF4 and the Exonuclease BGLF5 Have Opposite Effects on the Regulation of Viral Protein Production. J. Virol. 83: 10877-10891 [Abstract] [Full Text]  
  • Iwahori, S., Murata, T., Kudoh, A., Sato, Y., Nakayama, S., Isomura, H., Kanda, T., Tsurumi, T. (2009). Phosphorylation of p27Kip1 by Epstein-Barr Virus Protein Kinase Induces Its Degradation through SCFSkp2 Ubiquitin Ligase Actions during Viral Lytic Replication. J. Biol. Chem. 284: 18923-18931 [Abstract] [Full Text]  
  • Asai, R., Kato, A., Kawaguchi, Y. (2009). Epstein-Barr virus protein kinase BGLF4 interacts with viral transactivator BZLF1 and regulates its transactivation activity. J. Gen. Virol. 90: 1575-1581 [Abstract] [Full Text]  
  • Zhu, J., Liao, G., Shan, L., Zhang, J., Chen, M.-R., Hayward, G. S., Hayward, S. D., Desai, P., Zhu, H. (2009). Protein Array Identification of Substrates of the Epstein-Barr Virus Protein Kinase BGLF4. J. Virol. 83: 5219-5231 [Abstract] [Full Text]  
  • Wang, J.-T., Doong, S.-L., Teng, S.-C., Lee, C.-P., Tsai, C.-H., Chen, M.-R. (2009). Epstein-Barr Virus BGLF4 Kinase Suppresses the Interferon Regulatory Factor 3 Signaling Pathway. J. Virol. 83: 1856-1869 [Abstract] [Full Text]  
  • Lee, C.-P., Huang, Y.-H., Lin, S.-F., Chang, Y., Chang, Y.-H., Takada, K., Chen, M.-R. (2008). Epstein-Barr Virus BGLF4 Kinase Induces Disassembly of the Nuclear Lamina To Facilitate Virion Production. J. Virol. 82: 11913-11926 [Abstract] [Full Text]  
  • Sugimoto, K., Uema, M., Sagara, H., Tanaka, M., Sata, T., Hashimoto, Y., Kawaguchi, Y. (2008). Simultaneous Tracking of Capsid, Tegument, and Envelope Protein Localization in Living Cells Infected with Triply Fluorescent Herpes Simplex Virus 1. J. Virol. 82: 5198-5211 [Abstract] [Full Text]  
  • Yang, P.-W., Chang, S.-S., Tsai, C.-H., Chao, Y.-H., Chen, M.-R. (2008). Effect of phosphorylation on the transactivation activity of Epstein-Barr virus BMRF1, a major target of the viral BGLF4 kinase. J. Gen. Virol. 89: 884-895 [Abstract] [Full Text]  
  • Lu, C.-C., Chen, Y.-C., Wang, J.-T., Yang, P.-W., Chen, M.-R. (2007). Xeroderma pigmentosum C is involved in Epstein Barr virus DNA replication. J. Gen. Virol. 88: 3234-3243 [Abstract] [Full Text]  
  • Chiu, Y.-F., Tung, C.-P., Lee, Y.-H., Wang, W.-H., Li, C., Hung, J.-Y., Wang, C.-Y., Kawaguchi, Y., Liu, S.-T. (2007). A comprehensive library of mutations of Epstein Barr virus. J. Gen. Virol. 88: 2463-2472 [Abstract] [Full Text]  
  • Gershburg, E., Raffa, S., Torrisi, M. R., Pagano, J. S. (2007). Epstein-Barr Virus-Encoded Protein Kinase (BGLF4) Is Involved in Production of Infectious Virus. J. Virol. 81: 5407-5412 [Abstract] [Full Text]  
  • Lee, C.-P., Chen, J.-Y., Wang, J.-T., Kimura, K., Takemoto, A., Lu, C.-C., Chen, M.-R. (2007). Epstein-Barr Virus BGLF4 Kinase Induces Premature Chromosome Condensation through Activation of Condensin and Topoisomerase II. J. Virol. 81: 5166-5180 [Abstract] [Full Text]  
  • Izumiya, Y., Izumiya, C., Van Geelen, A., Wang, D.-H., Lam, K. S., Luciw, P. A., Kung, H.-J. (2007). Kaposi's Sarcoma-Associated Herpesvirus-Encoded Protein Kinase and Its Interaction with K-bZIP. J. Virol. 81: 1072-1082 [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»