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Journal of Virology, April 2007, p. 3229-3239, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02537-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Ubiquitous Cellular Transcriptional Factor USF Targets the Varicella-Zoster Virus Open Reading Frame 10 Promoter and Determines Virulence in Human Skin Xenografts in SCIDhu Mice In Vivo{triangledown}

Xibing Che,1* Barbara Berarducci,1 Marvin Sommer,1 William T. Ruyechan,2 and Ann M. Arvin1

Departments of Pediatrics and Microbiology & Immunology, Stanford University School of Medicine, Stanford, California,1 Department of Microbiology and Immunology, State University of New York at Buffalo, Buffalo, New York2

Received 17 November 2006/ Accepted 19 January 2007

Varicella-zoster virus (VZV) open reading frame 10 (ORF10) is a determinant of virulence in SCIDhu skin xenografts but not in human T cells in vivo. In this analysis of the regulation of ORF10 transcription, we have identified four ORF10-related transcripts, including a major 1.3-kb RNA spanning ORF10 only and three other read-through transcripts. Rapid-amplification-of-cDNA-ends experiments indicated that the 1.3-kb transcript of ORF10 has single initiation and termination sites. In transient expression assays, the ORF10 promoter was strongly stimulated by the major VZV transactivator, IE62. Deletion analyses revealed approximate boundaries for the full ORF10 promoter activity between –75 and –45 and between +5 and –8, relative to the ORF10 transcription start site. The recombinant virus POKA10-{Delta}pro, with the ORF10 promoter deletion, blocked transcription of ORF10 and also of ORF9A and ORF9 mRNAs, whereas expression of read-through ORF9A/9/10 and ORF9/10 transcripts was increased, compensating for the loss of the monocistronic mRNAs. The cellular factor USF bound specifically to its consensus site within the ORF10 promoter and was required for IE62 transactivation, whereas disrupting the predicted TATA boxes or Oct-1 binding elements had no effect. The USF binding site was disrupted in the recombinant virus, POKA10-pro{Delta}USF, and no ORF10 protein was produced. Both ORF10 promoter mutants reduced VZV replication in SCIDhu skin xenografts. These observations provided further evidence of the contribution of the ORF10 protein to VZV pathogenesis in skin and demonstrated that VZV depends upon the cellular transcriptional factor USF to support its virulence in human skin in vivo.

* Corresponding author. Mailing address: 300 Pasteur Drive, Rm. S356, Stanford University School of Medicine, Stanford, CA 94305-5208. Phone: (650) 723-6353. Fax: (650) 725-8040. E-mail: xibing{at}stanford.edu.

{triangledown} Published ahead of print on 24 January 2007.

Journal of Virology, April 2007, p. 3229-3239, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02537-06
Copyright © 2007, 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., 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]  
  • Zerboni, L., Reichelt, M., Jones, C. D., Zehnder, J. L., Ito, H., Arvin, A. M. (2007). From the Cover: Aberrant infection and persistence of varicella-zoster virus in human dorsal root ganglia in vivo in the absence of glycoprotein I. Proc. Natl. Acad. Sci. USA 104: 14086-14091 [Abstract] [Full Text]  


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