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

 Previous Article  |  Next Article 

Journal of Virology, September 2001, p. 8224-8239, Vol. 75, No. 17
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.17.8224-8239.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Mutational Analysis of the Repeated Open Reading Frames, ORFs 63 and 70 and ORFs 64 and 69, of Varicella-Zoster Virus

Marvin H. Sommer,1,* Edward Zagha,1 Oscar K. Serrano,1 Chia Chi Ku,1 Leigh Zerboni,1 Armin Baiker,1 Richard Santos,2 Mary Spengler,3 Jennifer Lynch,3 Charles Grose,2 William Ruyechan,3 John Hay,3 and Ann M. Arvin1

Department of Pediatrics, Stanford University School of Medicine, Stanford, California1; Department of Pediatrics, University of Iowa, Iowa City, Iowa2; and Department of Microbiology, State University of New York at Buffalo, Buffalo, New York3

Received 15 February 2001/Accepted 4 June 2001

Varicella-zoster virus (VZV) open reading frame 63 (ORF63), located between nucleotides 110581 and 111417 in the internal repeat region, encodes a nuclear phosphoprotein which is homologous to herpes simplex virus type 1 (HSV-1) ICP22 and is duplicated in the terminal repeat region as ORF70 (nucleotides 118480 to 119316). We evaluated the role of ORFs 63 and 70 in VZV replication, using recombinant VZV cosmids and PCR-based mutagenesis to make single and dual deletions of these ORFs. VZV was recovered within 8 to 10 days when cosmids with single deletions were transfected into melanoma cells along with the three intact VZV cosmids. In contrast, VZV was not detected in transfections carried out with a dual deletion cosmid. Infectious virus was recovered when ORF63 was cloned into a nonnative AvrII site in this cosmid, confirming that failure to generate virus was due to the dual ORF63/70 deletion and that replication required at least one gene copy. This requirement may be related to our observation that ORF63 interacts directly with ORF62, the major immediate-early transactivating protein of VZV. ORF64 is located within the inverted repeat region between nucleotides 111565 and 112107; it has some homology to the HSV-1 Us10 gene and is duplicated as ORF69 (nucleotides 117790 to 118332). ORF64 and ORF69 were deleted individually or simultaneously using the VZV cosmid system. Single deletions of ORF64 or ORF69 yielded viral plaques with the same kinetics and morphology as viruses generated with the parental cosmids. The dual deletion of ORF64 and ORF69 was associated with an abnormal plaque phenotype characterized by very large, multinucleated syncytia. Finally, all of the deletion mutants that yielded recombinants retained infectivity for human T cells in vitro and replicated efficiently in human skin in the SCIDhu mouse model of VZV pathogenesis.

* Corresponding author. Mailing address: 300 Pasteur Dr., Rm. G312, Stanford University School of Medicine, Stanford, CA 94305-5208. Phone: (650) 723-5682. Fax: (650) 725-8040. E-mail: marvman{at}stanford.edu.

Journal of Virology, September 2001, p. 8224-8239, Vol. 75, No. 17
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.17.8224-8239.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • 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]  
  • 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]  
  • Chaudhuri, V., Sommer, M., Rajamani, J., Zerboni, L., Arvin, A. M. (2008). Functions of Varicella-Zoster Virus ORF23 Capsid Protein in Viral Replication and the Pathogenesis of Skin Infection. J. Virol. 82: 10231-10246 [Abstract] [Full Text]  
  • Walters, M. S., Kyratsous, C. A., Wan, S., Silverstein, S. (2008). Nuclear Import of the Varicella-Zoster Virus Latency-Associated Protein ORF63 in Primary Neurons Requires Expression of the Lytic Protein ORF61 and Occurs in a Proteasome-Dependent Manner. J. Virol. 82: 8673-8686 [Abstract] [Full Text]  
  • Berarducci, B., Sommer, M., Zerboni, L., Rajamani, J., Arvin, A. M. (2007). Cellular and Viral Factors Regulate the Varicella-Zoster Virus gE Promoter during Viral Replication. J. Virol. 81: 10258-10267 [Abstract] [Full Text]  
  • Quinlivan, M. L., Gershon, A. A., Al Bassam, M. M., Steinberg, S. P., LaRussa, P., Nichols, R. A., Breuer, J. (2007). From the Cover: Natural selection for rash-forming genotypes of the varicella-zoster vaccine virus detected within immunized human hosts. Proc. Natl. Acad. Sci. USA 104: 208-212 [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]  
  • 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]  
  • Hood, C., Cunningham, A. L., Slobedman, B., Arvin, A. M., Sommer, M. H., Kinchington, P. R., Abendroth, A. (2006). Varicella-Zoster Virus ORF63 Inhibits Apoptosis of Primary Human Neurons. J. Virol. 80: 1025-1031 [Abstract] [Full Text]  
  • Schaap, A., Fortin, J.-F., Sommer, M., Zerboni, L., Stamatis, S., Ku, C.-C., Nolan, G. P., Arvin, A. M. (2005). T-Cell Tropism and the Role of ORF66 Protein in Pathogenesis of Varicella-Zoster Virus Infection. J. Virol. 79: 12921-12933 [Abstract] [Full Text]  
  • Kennedy, P. G. E., Grinfeld, E., Craigon, M., Vierlinger, K., Roy, D., Forster, T., Ghazal, P. (2005). Transcriptomal analysis of varicella-zoster virus infection using long oligonucleotide-based microarrays. J. Gen. Virol. 86: 2673-2684 [Abstract] [Full Text]  
  • Ito, H., Sommer, M. H., Zerboni, L., Baiker, A., Sato, B., Liang, R., Hay, J., Ruyechan, W., Arvin, A. M. (2005). Role of the Varicella-Zoster Virus Gene Product Encoded by Open Reading Frame 35 in Viral Replication In Vitro and in Differentiated Human Skin and T Cells In Vivo. J. Virol. 79: 4819-4827 [Abstract] [Full Text]  
  • Cohen, J. I., Krogmann, T., Bontems, S., Sadzot-Delvaux, C., Pesnicak, L. (2005). Regions of the Varicella-Zoster Virus Open Reading Frame 63 Latency-Associated Protein Important for Replication In Vitro Are Also Critical for Efficient Establishment of Latency. J. Virol. 79: 5069-5077 [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]  
  • 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]  
  • Cohen, J. I., Cox, E., Pesnicak, L., Srinivas, S., Krogmann, T. (2004). The Varicella-Zoster Virus Open Reading Frame 63 Latency-Associated Protein Is Critical for Establishment of Latency. J. Virol. 78: 11833-11840 [Abstract] [Full Text]  
  • Yang, M., Hay, J., Ruyechan, W. T. (2004). The DNA Element Controlling Expression of the Varicella-Zoster Virus Open Reading Frame 28 and 29 Genes Consists of Two Divergent Unidirectional Promoters Which Have a Common USF Site. J. Virol. 78: 10939-10952 [Abstract] [Full Text]  
  • Baiker, A., Fabel, K., Cozzio, A., Zerboni, L., Fabel, K., Sommer, M., Uchida, N., He, D., Weissman, I., Arvin, A. M. (2004). Varicella-zoster virus infection of human neural cells in vivo. Proc. Natl. Acad. Sci. USA 101: 10792-10797 [Abstract] [Full Text]  
  • Baiker, A., Bagowski, C., Ito, H., Sommer, M., Zerboni, L., Fabel, K., Hay, J., Ruyechan, W., Arvin, A. M. (2004). The Immediate-Early 63 Protein of Varicella-Zoster Virus: Analysis of Functional Domains Required for Replication In Vitro and for T-Cell and Skin Tropism in the SCIDhu Model In Vivo. J. Virol. 78: 1181-1194 [Abstract] [Full Text]  
  • Cohrs, R. J., Hurley, M. P., Gilden, D. H. (2003). Array Analysis of Viral Gene Transcription during Lytic Infection of Cells in Tissue Culture with Varicella-Zoster Virus. J. Virol. 77: 11718-11732 [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]  
  • Jones, J. O., Arvin, A. M. (2002). Microarray Analysis of Host Cell Gene Transcription in Response to Varicella-Zoster Virus Infection of Human T Cells and Fibroblasts In Vitro and SCIDhu Skin Xenografts In Vivo. J. Virol. 77: 1268-1280 [Abstract] [Full Text]  
  • Ito, H., Sommer, M. H., Zerboni, L., He, H., Boucaud, D., Hay, J., Ruyechan, W., Arvin, A. M. (2002). Promoter Sequences of Varicella-Zoster Virus Glycoprotein I Targeted by Cellular Transactivating Factors Sp1 and USF Determine Virulence in Skin and T Cells in SCIDhu Mice In Vivo. J. Virol. 77: 489-498 [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»