乙型肝炎病毒的复制需要钙依赖性 HBx 诱导的肝细胞 G1 期停滞。
Replication of the hepatitis B virus requires a calcium-dependent HBx-induced G1 phase arrest of hepatocytes.
机构信息
Graduate Program in Molecular and Cellular Biology and Genetics, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
出版信息
Virology. 2010 Nov 10;407(1):14-25. doi: 10.1016/j.virol.2010.07.042. Epub 2010 Aug 16.
Abstract
Chronic HBV infections cause hepatocellular carcinoma (HCC). Activities of the HBV HBx protein regulate HBV replication and may contribute to the development of HCC. We previously reported that HBx causes primary rat hepatocytes to exit G0 but stall in G1 phase of the cell cycle; entry into G1 stimulated HBV replication. We now report that the activity of the mitochondria permeability transition pore is required for HBx regulation of cell cycle proteins and HBV replication in primary rat hepatocytes, that progression from G0 to G1 stimulates HBV polymerase activity, and that HBV replication is facilitated by the HBx-induced G1 arrest. HBx stimulation of HBV replication was linked to elevation of the R2 subunit of ribonucleotide reductase. Our studies suggest that HBx uses mitochondrial-dependent calcium signaling to cause hepatocytes to exit G0 but stall in G1 and that this HBx activity alters the cellular environment and stimulates HBV replication.
摘要
慢性 HBV 感染可导致肝细胞癌（HCC）。HBV HBx 蛋白的活性调节 HBV 复制，并可能有助于 HCC 的发展。我们之前的研究表明，HBx 导致原代大鼠肝细胞退出 G0 期，但在细胞周期的 G1 期停滞；进入 G1 期可刺激 HBV 复制。我们现在报告称，线粒体通透性转换孔的活性是 HBx 调节原代大鼠肝细胞细胞周期蛋白和 HBV 复制所必需的，从 G0 到 G1 的进展刺激 HBV 聚合酶活性，HBx 诱导的 G1 期阻滞促进了 HBV 复制。HBx 对 HBV 复制的刺激与核苷酸还原酶 R2 亚基的升高有关。我们的研究表明，HBx 利用线粒体依赖性钙信号导致肝细胞退出 G0 期但在 G1 期停滞，而这种 HBx 活性改变了细胞环境并刺激了 HBV 复制。
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本文引用的文献
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Hepatitis B virus activates deoxynucleotide synthesis in nondividing hepatocytes by targeting the R2 gene.乙型肝炎病毒通过靶向 R2 基因激活非分裂肝细胞中的脱氧核苷酸合成。
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The hepatitis B virus X protein modulates hepatocyte proliferation pathways to stimulate viral replication.乙型肝炎病毒 X 蛋白调节肝细胞增殖途径以刺激病毒复制。
J Virol. 2010 Mar;84(6):2675-86. doi: 10.1128/JVI.02196-09. Epub 2010 Jan 6.
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Hepatitis B virus X protein molecular functions and its role in virus life cycle and pathogenesis.乙型肝炎病毒X蛋白的分子功能及其在病毒生命周期和发病机制中的作用。
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6
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Modulation of MAPK pathways and cell cycle by replicating hepatitis B virus: factors contributing to hepatocarcinogenesis.复制型乙型肝炎病毒对丝裂原活化蛋白激酶（MAPK）信号通路和细胞周期的调控：对肝癌发生的影响因素
J Hepatol. 2007 Sep;47(3):325-37. doi: 10.1016/j.jhep.2007.03.025. Epub 2007 Apr 18.
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Enhancement of hepatitis B virus replication by the regulatory X protein in vitro and in vivo.调节性X蛋白在体外和体内增强乙型肝炎病毒复制
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10
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