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Journal of Virology, December 2008, p. 12154-12163, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01693-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Varicella-Zoster Virus IE62 Protein Utilizes the Human Mediator Complex in Promoter Activation{triangledown}

Min Yang, John Hay, and William T. Ruyechan*

Department of Microbiology and Immunology and Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, Buffalo, New York

Received 8 August 2008/ Accepted 29 September 2008

The varicella-zoster virus (VZV) major transactivator, IE62, is involved in the expression of all kinetic classes of VZV genes and can also activate cellular promoters, promoters from heterologous viruses, and artificial promoters containing only TATA elements. A key component of the mechanism of IE62 transactivation is an acidic activation domain comprising the N-terminal 86 amino acids of IE62. However, the cellular target of this N-terminal acidic activation is unknown. In the work presented here, we show that the IE62 activation domain targets the human Mediator complex via the Med25 (ARC92) subunit and that this interaction appears to be fundamental for transactivation by the IE62 activation domain. In contrast, the Med23 subunit (Sur2/TRAP150β/DRIP130/CRSP130) of the Mediator complex is not essential for IE62-mediated activation. Further, the IE62 activation domain appears to selectively interact with a form of the Mediator complex lacking CDK8. Chromatin immunoprecipitation experiments showed that IE62 stimulates recruitment of Mediator to an IE62-responsive model promoter. Finally, immunofluorescence microscopy of VZV-infected cells demonstrated intranuclear translocation of the Mediator complex to viral replication compartments. These studies suggest that Mediator is an essential component for efficient VZV gene expression.


* Corresponding author. Mailing address: Department of Microbiology, 138 Farber Hall, University at Buffalo, SUNY, Buffalo, NY 14214. Phone: (716) 829-2312. Fax: (716) 829-2376. E-mail: ruyechan{at}buffalo.edu

{triangledown} Published ahead of print on 8 October 2008.


Journal of Virology, December 2008, p. 12154-12163, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01693-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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  • Kidd, B. N., Edgar, C. I., Kumar, K. K., Aitken, E. A., Schenk, P. M., Manners, J. M., Kazan, K. (2009). The Mediator Complex Subunit PFT1 Is a Key Regulator of Jasmonate-Dependent Defense in Arabidopsis. Plant Cell 21: 2237-2252 [Abstract] [Full Text]  
  • Yamamoto, S., Eletsky, A., Szyperski, T., Hay, J., Ruyechan, W. T. (2009). Analysis of the Varicella-Zoster Virus IE62 N-Terminal Acidic Transactivating Domain and Its Interaction with the Human Mediator Complex. J. Virol. 83: 6300-6305 [Abstract] [Full Text]