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Journal of Virology, November 2009, p. 11116-11122, Vol. 83, No. 21
0022-538X/09/$08.00+0     doi:10.1128/JVI.00512-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Functional Interaction between Epstein-Barr Virus Replication Protein Zta and Host DNA Damage Response Protein 53BP1 {triangledown} ,{dagger}

Sarah G. Bailey,1 Elizabeth Verrall,1 Celine Schelcher,1 Alex Rhie,2 Aidan J. Doherty,2 and Alison J. Sinclair1*

The School of Life Sciences,1 Genome Damage and Stability Centre, University of Sussex, Brighton, East Sussex BN1 9QG, United Kingdom2

Received 12 March 2009/ Accepted 26 July 2009

Epstein-Barr virus (EBV; human herpesvirus 4) poses major clinical problems worldwide. Following primary infection, EBV enters a form of long-lived latency in B lymphocytes, expressing few viral genes, and it persists for the lifetime of the host with sporadic bursts of viral replication. The switch between latency and replication is governed by the action of a multifunctional viral protein Zta (also called BZLF1, ZEBRA, and Z). Using a global proteomic approach, we identified a host DNA damage repair protein that specifically interacts with Zta: 53BP1. 53BP1 is intimately connected with the ATM signal transduction pathway, which is activated during EBV replication. The interaction of 53BP1 with Zta requires the C-terminal ends of both proteins. A series of Zta mutants that show a wild-type ability to perform basic functions of Zta, such as dimer formation, interaction with DNA, and the transactivation of viral genes, were shown to have lost the ability to induce the viral lytic cycle. Each of these mutants also is compromised in the C-terminal region for interaction with 53BP1. In addition, the knockdown of 53BP1 expression reduced viral replication, suggesting that the association between Zta and 53BP1 is involved in the viral replication cycle.

* Corresponding author. Mailing address: Biochemistry & Biomedical Science, School of Life Sciences, John Maynard Smith Building, University of Sussex, Brighton BN1 9QG, United Kingdom. Phone: (44) 1273 678 194. Fax: (44) 1273 678 433. E-mail: a.j.sinclair{at}sussex.ac.uk

{triangledown} Published ahead of print on 5 August 2009.

{dagger} The authors have paid a fee to allow immediate free access to this article.

Journal of Virology, November 2009, p. 11116-11122, Vol. 83, No. 21
0022-538X/09/$08.00+0     doi:10.1128/JVI.00512-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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