乙型肝炎病毒调节 HBx 蛋白与 DDB1 的结合对于最大程度地复制 HBV 是必需的，但不是充分的。
Hepatitis B virus regulatory HBx protein binding to DDB1 is required but is not sufficient for maximal HBV replication.
机构信息
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
出版信息
Virology. 2012 Apr 25;426(1):73-82. doi: 10.1016/j.virol.2012.01.021. Epub 2012 Feb 17.
Abstract
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.
摘要
HBx 蛋白可刺激乙型肝炎病毒（HBV）的稳定复制。HBx 可与细胞蛋白 DDB1 结合，但这种相互作用对 HBV 复制的重要性尚不清楚。我们使用 HepG2 细胞中的基于质粒的复制测定来测试 HBx 与 DDB1 结合是否是 HBV 复制所必需的。三个 DDB1 结合缺陷的 HBx 点突变体（HBx(69)、HBx(90/91)、HBx(R96E)）无法从 HBx 缺陷型质粒中恢复野生型复制水平，这确立了 HBx-DDB1 相互作用对于 HBV 复制的最大作用。重叠 HBx 截断突变体的分析表明，HBx-DDB1 结合域和羧基区域都需要在体外和体内进行最大 HBV 复制，这表明 HBx-DDB1 相互作用可募集对复制至关重要的调节功能。最后，我们证明 HBx 定位于 Cul4A-DDB1 复合物，并讨论了其对 HBV 复制模型的可能影响。
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