Structural organization of the hepatitis B virus minichromosome.
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.
Department of Gastroenterology and Hepatology, Medical School Hannover, Hannover, Germany. Thomas.Bock@med.uni-tuebingen.de
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Schwinn
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Locarnini
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Manns
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D002843:Chromatin / Q000737:chemistry; D004270:DNA, Circular / Q000737:chemistry* / Q000648:ultrastructure; D004279:DNA, Viral / Q000737:chemistry* / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism; D006515:Hepatitis B virus / Q000737:chemistry / Q000235:genetics*; D008970:Molecular Weight; D009690:Nucleic Acid Conformation; D009698:Nucleoproteins / Q000737:chemistry / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry; D013211:Staphylococcus aureus / Q000201:enzymology; D014758:Viral Core Proteins / Q000737:chemistry / Q000378:metabolism
D002843:Chromatin; D004270:DNA, Circular; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D009698:Nucleoproteins; D009707:Nucleosomes; D014758:Viral Core Proteins; D003851:Deoxyribonucleases