Hepatitis B virus regulatory HBx protein binding to DDB1 is required but is not sufficient for maximal HBV replication

被引：81

作者：

Hodgson, Amanda J. ^{[1
]}

Hyser, Joseph M. ^{[1
]}

Keasler, Victor V. ^{[1
]}

Cang, Yong ^{[2
]}

Slagle, Betty L. ^{[1
]}

机构：

[1] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA

[2] Sanford Burnham Med Res Inst, Signal Transduct Program, La Jolla, CA 92037 USA

来源：

VIROLOGY | 2012年 / 426卷 / 01期

关键词：

Hepatitis B virus; HBx; DDB1; HBV replication; VIRAL X PROTEIN; CELL-CYCLE; GENOME REPLICATION; DNA-REPAIR; V PROTEIN; GENE; TRANSACTIVATION; INTERACTS; ACTIVATION; NUCLEAR;

D O I：

10.1016/j.virol.2012.01.021

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Robust hepatitis B virus (HBV) replication is stimulated by the regulatory HBx protein. HBx binds the cellular protein DDB1; however, the importance of this interaction for HBV replication remains unknown. We tested whether HBx binding to DDB1 was required for HBV replication using a plasmid based replication assay in HepG2 cells. Three DDB1 binding-deficient HBx point mutants (HBx(69), HBx(90/91), HBx(R96E)) failed to restore wildtype levels of replication from an HBx-deficient plasmid, which established the importance of the HBx-DDB1 interaction for maximal HBV replication. Analysis of overlapping HBx truncation mutants revealed that both the HBx-DDB1 binding domain and the carboxyl region are required for maximal HBV replication both in vitro and in vivo, suggesting the HBx-DDB1 interaction recruits regulatory functions critical for replication. Finally we demonstrate that HBx localizes to the Cul4A-DDB1 complex, and discuss the possible implications for models of HBV replication. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：73 / 82

页数：10

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