Bock C T, Schwinn S, Locarnini S, Fyfe J, Manns M P, Trautwein C, Zentgraf H
Department of Gastroenterology and Hepatology, Medical School Hannover, Hannover, Germany.
J Mol Biol. 2001 Mar 16;307(1):183-96. doi: 10.1006/jmbi.2000.4481.
The replicative intermediate of hepatitis B virus (HBV), the covalently closed, circular DNA, is organized into minichromosomes in the nucleus of the infected cell by histone and non-histone proteins. In this study we investigated the architecture of the HBV minichromosome in more detail. In contrast to cellular chromatin the nucleosomal spacing of the HBV minichromosome has been shown to be unusually reduced by approximately 10 %. A potential candidate responsible for an alteration in the chromatin structure of the HBV minichromosome is the HBV core protein. The HBV core protein has been implicated in the nuclear targeting process of the viral genome. The association of the HBV core protein with nuclear HBV replicative intermediates could strengthen this role. Our findings, confirmed by in vivo and in vitro experiments indicate that HBV core protein is a component of the HBV minichromosome, binds preferentially to HBV double-stranded DNA, and its binding results in a reduction of the nucleosomal spacing of the HBV nucleoprotein complexes by 10 %. From this model of the HBV minichromosome we propose that the HBV core protein may have an impact on the nuclear targeting of the HBV genome and be involved in viral transcription by regulating the nucleosomal arrangement of the HBV regulatory elements, probably in a positive manner.
乙型肝炎病毒（HBV）的复制中间体，即共价闭合环状DNA，在感染细胞的细胞核中通过组蛋白和非组蛋白组装成微型染色体。在本研究中，我们更详细地研究了HBV微型染色体的结构。与细胞染色质不同，HBV微型染色体的核小体间距已被证明异常缩短了约10%。HBV核心蛋白可能是导致HBV微型染色体染色质结构改变的一个潜在因素。HBV核心蛋白与病毒基因组的核靶向过程有关。HBV核心蛋白与核内HBV复制中间体的结合可能会强化这一作用。我们的研究结果经体内和体外实验证实，表明HBV核心蛋白是HBV微型染色体的一个组成部分，优先结合HBV双链DNA，其结合导致HBV核蛋白复合物的核小体间距减少10%。基于这个HBV微型染色体模型，我们提出HBV核心蛋白可能影响HBV基因组的核靶向，并可能通过调节HBV调控元件的核小体排列以一种积极的方式参与病毒转录。
