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

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• 作者：Authors ; Amanda J. Hodgson^a ; ¹ ; Joseph M. Hyser^a ; Victor V. Keasler^a ; ² ; Yong Cang^b ; Betty L. Slagle^a ; ^{bslagle@bcm.edu}
• 关键词：Hepatitis B virus ; HBx ; DDB1 ; HBV replication
• 刊名：Virology
• 出版年：2012
• 期刊代码：108_00426822
• 类别：imm
• 出版时间：25 April, 2012
• 卷：426
• 期：1
• 页码：73-82
• 文件大小：1087 K

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 (HBx⁶⁹, 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.