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 Schaap, A.
Right arrow Articles by Arvin, A. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schaap, A.
Right arrow Articles by Arvin, A. M.

 Previous Article  |  Next Article 

Journal of Virology, October 2005, p. 12921-12933, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12921-12933.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

T-Cell Tropism and the Role of ORF66 Protein in Pathogenesis of Varicella-Zoster Virus Infection

Anne Schaap,1* Jean-Francois Fortin,2 Marvin Sommer,1 Leigh Zerboni,1 Shaye Stamatis,1 Chia-Chi Ku,1 Garry P. Nolan,2 and Ann M. Arvin1,2

Departments of Pediatrics,1 Microbiology and Immunology, Stanford University School of Medicine, 300 Pasteur Dr., Stanford, California 94305-52082

Received 23 February 2005/ Accepted 25 July 2005

The pathogenesis of varicella-zoster virus (VZV) involves a cell-associated viremia during which infectious virus is carried from sites of respiratory mucosal inoculation to the skin. We now demonstrate that VZV infection of T cells is associated with robust virion production and modulation of the apoptosis and interferon pathways within these cells. The VZV serine/threonine protein kinase encoded by ORF66 is essential for the efficient replication of VZV in T cells. Preventing ORF66 protein expression by stop codon insertion (pOka66S) impaired the growth of the parent Oka (pOka) strain in T cells in SCID-hu T-cell xenografts in vivo and reduced formation of VZV virions. The lack of ORF66 protein also increased the susceptibility of infected T cells to apoptosis and reduced the capacity of the virus to interfere with induction of the interferon (IFN) signaling pathway following exposure to IFN-{gamma}. However, preventing ORF66 protein expression only slightly reduced growth in melanoma cells in culture and did not diminish virion formation in these cells. The pOka66S virus showed only a slight defect in growth in SCID-hu skin implants compared with intact pOka. These observations suggest that the ORF66 kinase plays a unique role during infection of T cells and supports VZV T-cell tropism by contributing to immune evasion and enhancing survival of infected T cells.

* Corresponding author. Mailing address: G312, Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Dr., Stanford, CA 94305-5208. Phone: (650) 725-6555. Fax: (650) 725-8040. E-mail: aschaap{at}stanford.edu.

Journal of Virology, October 2005, p. 12921-12933, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12921-12933.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Walters, M. S., Erazo, A., Kinchington, P. R., Silverstein, S. (2009). Histone Deacetylases 1 and 2 Are Phosphorylated at Novel Sites during Varicella-Zoster Virus Infection. J. Virol. 83: 11502-11513 [Abstract] [Full Text]  
  • Wang, L., Sommer, M., Rajamani, J., Arvin, A. M. (2009). Regulation of the ORF61 Promoter and ORF61 Functions in Varicella-Zoster Virus Replication and Pathogenesis. J. Virol. 83: 7560-7572 [Abstract] [Full Text]  
  • Oliver, S. L., Sommer, M., Zerboni, L., Rajamani, J., Grose, C., Arvin, A. M. (2009). Mutagenesis of Varicella-Zoster Virus Glycoprotein B: Putative Fusion Loop Residues Are Essential for Viral Replication, and the Furin Cleavage Motif Contributes to Pathogenesis in Skin Tissue In Vivo. J. Virol. 83: 7495-7506 [Abstract] [Full Text]  
  • Leisenfelder, S. A., Kinchington, P. R., Moffat, J. F. (2008). Cyclin-Dependent Kinase 1/Cyclin B1 Phosphorylates Varicella-Zoster Virus IE62 and Is Incorporated into Virions. J. Virol. 82: 12116-12125 [Abstract] [Full Text]  
  • Yang, M., Hay, J., Ruyechan, W. T. (2008). Varicella-Zoster Virus IE62 Protein Utilizes the Human Mediator Complex in Promoter Activation. J. Virol. 82: 12154-12163 [Abstract] [Full Text]  
  • Erazo, A., Yee, M. B., Osterrieder, N., Kinchington, P. R. (2008). Varicella-Zoster Virus Open Reading Frame 66 Protein Kinase Is Required for Efficient Viral Growth in Primary Human Corneal Stromal Fibroblast Cells. J. Virol. 82: 7653-7665 [Abstract] [Full Text]  
  • Eisfeld, A. J., Yee, M. B., Erazo, A., Abendroth, A., Kinchington, P. R. (2007). Downregulation of Class I Major Histocompatibility Complex Surface Expression by Varicella-Zoster Virus Involves Open Reading Frame 66 Protein Kinase-Dependent and -Independent Mechanisms. J. Virol. 81: 9034-9049 [Abstract] [Full Text]  
  • Schaap-Nutt, A., Sommer, M., Che, X., Zerboni, L., Arvin, A. M. (2006). ORF66 Protein Kinase Function Is Required for T-Cell Tropism of Varicella-Zoster Virus In Vivo. J. Virol. 80: 11806-11816 [Abstract] [Full Text]  
  • Finnen, R. L., Mizokami, K. R., Banfield, B. W., Cai, G.-Y., Simpson, S. A., Pizer, L. I., Levin, M. J. (2006). Postentry events are responsible for restriction of productive varicella-zoster virus infection in chinese hamster ovary cells.. J. Virol. 80: 10325-10334 [Abstract] [Full Text]  
  • Che, X., Zerboni, L., Sommer, M. H., Arvin, A. M. (2006). Varicella-zoster virus open reading frame 10 is a virulence determinant in skin cells but not in T cells in vivo.. J. Virol. 80: 3238-3248 [Abstract] [Full Text]  
  • Eisfeld, A. J., Turse, S. E., Jackson, S. A., Lerner, E. C., Kinchington, P. R. (2006). Phosphorylation of the Varicella-Zoster Virus (VZV) Major Transcriptional Regulatory Protein IE62 by the VZV Open Reading Frame 66 Protein Kinase. J. Virol. 80: 1710-1723 [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»