Functional Interaction between Epstein-Barr Virus Replication Protein Zta and Host DNA Damage Response Protein 53BP1

被引:34
作者
Bailey, Sarah G. [1 ]
Verrall, Elizabeth [1 ]
Schelcher, Celine [1 ]
Rhie, Alex [2 ]
Doherty, Aidan J. [2 ]
Sinclair, Alison J. [1 ]
机构
[1] Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England
[2] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9QG, E Sussex, England
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
IMMEDIATE-EARLY PROTEIN; DEPENDENT KINASE INHIBITORS; TRANSCRIPTION FACTOR ZTA; CREB-BINDING-PROTEIN; CELL-GROWTH ARREST; LYTIC CYCLE; ZEBRA PROTEIN; GENE-PRODUCT; HUMAN GAMMAHERPESVIRUSES; BZLF1; TRANSACTIVATOR;
D O I
10.1128/JVI.00512-09
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:11116 / 11122
页数:7
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