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 Kenyon, T. K.
Right arrow Articles by Grose, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kenyon, T. K.
Right arrow Articles by Grose, C.

 Previous Article  |  Next Article 

Journal of Virology, November 2002, p. 10980-10993, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.10980-10993.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Phosphorylation by the Varicella-Zoster Virus ORF47 Protein Serine Kinase Determines whether Endocytosed Viral gE Traffics to the trans-Golgi Network or Recycles to the Cell Membrane

T. K. Kenyon,1 Jeffrey I. Cohen,2 and Charles Grose1*

Department of Microbiology, University of Iowa, Iowa City, Iowa 52242,1 Medical Virology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 208922

Received 30 April 2002/ Accepted 3 July 2002

Like all alphaherpesviruses, varicella-zoster virus (VZV) infection proceeds by both cell-cell spread and virion production. Virions are enveloped within vacuoles located near the trans-Golgi network (TGN), while in cell-cell spread, surface glycoproteins fuse cells into syncytia. In this report, we delineate a potential role for serine/threonine phosphorylation of the cytoplasmic tail of the predominant VZV glycoprotein, gE, in these processes. The fact that VZV gE (formerly called gpI) is phosphorylated has been documented (E. A. Montalvo and C. Grose, Proc. Natl. Acad. Sci. USA 83:8967-8971, 1986), although respective roles of viral and cellular protein kinases have never been delineated. VZV ORF47 is a viral serine protein kinase that recognized a consensus sequence similar to that of casein kinase II (CKII). During open reading frame 47 (ORF47)-specific in vitro kinase assays, ORF47 phosphorylated four residues in the cytoplasmic tail of VZV gE (S593, S595, T596, and T598), thus modifying the known phosphofurin acidic cluster sorting protein 1 domain. CKII phosphorylated gE predominantly on the two threonine residues. In wild-type-virus-infected cells, where ORF47-mediated phosphorylation predominated, gE endocytosed and relocalized to the TGN. In cells infected with a VZV ORF47-null mutant, internalized VZV gE recycled to the plasma membrane and did not localize to the TGN. The mutant virus also formed larger syncytia than the wild-type virus, linking CKII-mediated gE phosphorylation with increased cell-cell spread. Thus, ORF47 and CKII behaved as "team players" in the phosphorylation of VZV gE. Taken together, the results showed that phosphorylation of VZV gE by ORF47 or CKII determined whether VZV infection proceeded toward a pathway likely involved with either virion production or cell-cell spread.

* Corresponding author. Mailing address: University Hospital/2501 JCP, 200 Hawkins Dr., Iowa City, IA 52242. Phone: (319) 356-2270. Fax: (319) 356-4855. E-mail: charles-grose{at}uiowa.edu.

Journal of Virology, November 2002, p. 10980-10993, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.10980-10993.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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]  
  • Berarducci, B., Rajamani, J., Reichelt, M., Sommer, M., Zerboni, L., Arvin, A. M. (2009). Deletion of the First Cysteine-Rich Region of the Varicella-Zoster Virus Glycoprotein E Ectodomain Abolishes the gE and gI Interaction and Differentially Affects Cell-Cell Spread and Viral Entry. J. Virol. 83: 228-240 [Abstract] [Full Text]  
  • Berarducci, B., Ikoma, M., Stamatis, S., Sommer, M., Grose, C., Arvin, A. M. (2006). Essential Functions of the Unique N-Terminal Region of the Varicella-Zoster Virus Glycoprotein E Ectodomain in Viral Replication and in the Pathogenesis of Skin Infection. J. Virol. 80: 9481-9496 [Abstract] [Full Text]  
  • Leisenfelder, S. A., Moffat, J. F. (2006). Varicella-zoster virus infection of human foreskin fibroblast cells results in atypical cyclin expression and cyclin-dependent kinase activity.. J. Virol. 80: 5577-5587 [Abstract] [Full Text]  
  • Lee, G. E., Murray, J. W., Wolkoff, A. W., Wilson, D. W. (2006). Reconstitution of Herpes Simplex Virus Microtubule-Dependent Trafficking In Vitro. J. Virol. 80: 4264-4275 [Abstract] [Full Text]  
  • Ku, C.-C., Besser, J., Abendroth, A., Grose, C., Arvin, A. M. (2005). Varicella-Zoster Virus Pathogenesis and Immunobiology: New Concepts Emerging from Investigations with the SCIDhu Mouse Model. J. Virol. 79: 2651-2658 [Full Text]  
  • Maresova, L., Pasieka, T. J., Homan, E., Gerday, E., Grose, C. (2005). Incorporation of Three Endocytosed Varicella-Zoster Virus Glycoproteins, gE, gH, and gB, into the Virion Envelope. J. Virol. 79: 997-1007 [Abstract] [Full Text]  
  • Besser, J., Ikoma, M., Fabel, K., Sommer, M. H., Zerboni, L., Grose, C., Arvin, A. M. (2004). Differential Requirement for Cell Fusion and Virion Formation in the Pathogenesis of Varicella-Zoster Virus Infection in Skin and T Cells. J. Virol. 78: 13293-13305 [Abstract] [Full Text]  
  • Moffat, J., Mo, C., Cheng, J. J., Sommer, M., Zerboni, L., Stamatis, S., Arvin, A. M. (2004). Functions of the C-Terminal Domain of Varicella-Zoster Virus Glycoprotein E in Viral Replication In Vitro and Skin and T-Cell Tropism In Vivo. J. Virol. 78: 12406-12415 [Abstract] [Full Text]  
  • Ye, M., Morello, C. S., Spector, D. H. (2004). Multiple Epitopes in the Murine Cytomegalovirus Early Gene Product M84 Are Efficiently Presented in Infected Primary Macrophages and Contribute to Strong CD8+-T-Lymphocyte Responses and Protection following DNA Immunization. J. Virol. 78: 11233-11245 [Abstract] [Full Text]  
  • Taylor, S. L., Kinchington, P. R., Brooks, A., Moffat, J. F. (2004). Roscovitine, a Cyclin-Dependent Kinase Inhibitor, Prevents Replication of Varicella-Zoster Virus. J. Virol. 78: 2853-2862 [Abstract] [Full Text]  
  • Pasieka, T. J., Maresova, L., Shiraki, K., Grose, C. (2004). Regulation of Varicella-Zoster Virus-Induced Cell-to-Cell Fusion by the Endocytosis-Competent Glycoproteins gH and gE. J. Virol. 78: 2884-2896 [Abstract] [Full Text]  
  • Jarvis, M. A., Jones, T. R., Drummond, D. D., Smith, P. P., Britt, W. J., Nelson, J. A., Baldick, C. J. (2004). Phosphorylation of Human Cytomegalovirus Glycoprotein B (gB) at the Acidic Cluster Casein Kinase 2 Site (Ser900) Is Required for Localization of gB to the trans-Golgi Network and Efficient Virus Replication. J. Virol. 78: 285-293 [Abstract] [Full Text]  
  • Sato, H., Pesnicak, L., Cohen, J. I. (2003). Varicella-Zoster Virus ORF47 Protein Kinase, Which Is Required for Replication in Human T Cells, and ORF66 Protein Kinase, Which Is Expressed during Latency, Are Dispensable for Establishment of Latency. J. Virol. 77: 11180-11185 [Abstract] [Full Text]  
  • Sato, B., Ito, H., Hinchliffe, S., Sommer, M. H., Zerboni, L., Arvin, A. M. (2003). Mutational Analysis of Open Reading Frames 62 and 71, Encoding the Varicella-Zoster Virus Immediate-Early Transactivating Protein, IE62, and Effects on Replication In Vitro and in Skin Xenografts in the SCID-hu Mouse In Vivo. J. Virol. 77: 5607-5620 [Abstract] [Full Text]  
  • Besser, J., Sommer, M. H., Zerboni, L., Bagowski, C. P., Ito, H., Moffat, J., Ku, C.-C., Arvin, A. M. (2003). Differentiation of Varicella-Zoster Virus ORF47 Protein Kinase and IE62 Protein Binding Domains and Their Contributions to Replication in Human Skin Xenografts in the SCID-hu Mouse. J. Virol. 77: 5964-5974 [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»