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Published online ahead of print on 4 March 2009 as doi:10.1099/vir.0.007922-0
Journal of General Virology 2009;90:1450.

A more recent version of this article appeared on June 1, 2009 J Gen Virol (2009), DOI 10.1099/vir.0.007922-0
© 2009 Society for General Microbiology

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The Epstein-Barr Virus Lytic Cycle Activator Zta Interacts With Methylated ZRE In Promoter Of Host Target Gene Egr1

James Heather, Kirsty Flower, Samine Isaac and Alison J. Sinclair1

University of Sussex

1 E-mail: a.j.sinclair{at}sussex.ac.uk

Activation of the host gene egr1 is essential for the lytic replication of Epstein-Barr virus (EBV). Egr1 is activated by Zta (BZLF1, ZEBRA). Zta interacts directly with DNA through a series of closely related Zta-response elements (ZREs). Here we dissect the mechanism used by Zta to interact with the egr1 promoter and identify a weak interaction with egr1ZRE that is dependent on the distal part of egr1ZRE. Furthermore, we demonstrate that the ability of Zta to interact with egr1ZRE is enhanced at least ten-fold by methylation. The ability of Zta to transactivate a reporter construct driven by the egr1 promoter can be enhanced by methylation. As the ability of Zta to interact with a methylated ZRE in the EBV genome correlates with its ability to activate the expression of the endogenous viral gene BRLF1, this suggests that Zta may also have the capability to overturn epigenetic control of egr1.

Received 14 October 2008; accepted 20 February 2009.





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