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Functional interaction between Epstein-Barr virus replication protein Zta and host DNA damage response protein 53BP1

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posted on 2023-06-07, 23:34 authored by Sarah G Bailey, Elizabeth Verrall, Celine Schelcher, Alex Rhie, Aidan DohertyAidan Doherty, Alison Sinclair
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Journal of Virology

ISSN

0022-538X

Publisher

American Society for Microbiology

Issue

21

Volume

83

Page range

11116-11122

Department affiliated with

  • Biochemistry Publications

Notes

Main author, majority of research undertaken my my research group. Collaboration for reagents with another group at University of Sussex.

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

First Open Access (FOA) Date

2017-11-15

First Compliant Deposit (FCD) Date

2017-11-15

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