Role of HBx Protein in HBV Replication

描述（由申请人提供）：本提案的长期目标 目的是了解B型肝炎病毒（HBV）HBx基因在病毒感染中的作用， 感染请注意，该补助金的名称已从 从“B型肝炎病毒HBx蛋白的转录和转化”到”作用 HBx蛋白在HBV复制中的作用”，以反映我们对 HBx。 目的1：人B肝炎病毒（HBV）HBx蛋白的分子机制 行动上HBx激活细胞质信号转导通路。HBx激活 Pyk 2-Src酪氨酸激酶信号通路的表达代表了一个重要的 在肝细胞系中的病毒复制活性。研究概述 了解HBx激活Pyk 2-Src信号的分子机制 转导，因为它与病毒的HBx刺激紧密相关。 复制的此外，HBx似乎具有可能 刺激病毒转录。研究还将通过以下方式调查其机制： HBx在病毒转录中起作用，包括在 细胞核及其对病毒复制的影响。 目的2：HBx蛋白在HBV复制中的作用。建议进行研究以确定 HBx激活HBV逆转录和DNA的分子基础 复制的已经开发了用于递送嗜肝DNA病毒的模型系统 分化的肝细胞系和啮齿动物原代肝细胞 在培养中，其允许病毒以HBx依赖性方式复制。研究 将研究HBx在病毒复制中的作用， 相关系统，重点是HBx诱导HBV核心蛋白磷酸化， 控制细胞周期和诱导核苷酸代谢。 还将在原代肝细胞中研究HBx依赖性HBV复制 从影响HBV复制的基因缺陷的小鼠制备， 包括Src和Pyk 2激酶的敲除，以更好地了解它们的功能。 病毒复制的重要性。

DESCRIPTION (provided by applicant): The long term objectives of this proposal are to understand the roles of the hepatitis B virus (HBV) HBx gene in viral infection. Please note that the title of this grant has been changed from "Transcription and Transformation by Hepatitis B Virus HBx Protein," to" Role of HBx protein in HBV replication" to reflect the progression of our studies on HBx. AIM 1: Molecular mechanism for human hepatitis B virus (HBV) HBx protein action. HBx activates cytoplasmic signal transduction pathways. HBx activation of the Pyk2-Src tyrosine kinase signalling pathway represents an important activity for viral replication in hepatocytic cell lines. Studies are outlined to understand the molecular mechanism for HBx activation of Pyk2-Src signal transduction, since it is tightly linked to HBx stimulation of viral replication. In addition, HBx appears to possess nuclear functions that may stimulate viral transcription. Studies will also investigate the mechanism by which HBx functions in viral transcription, including a possible role in the nucleus, and its impact on viral replication. AIM 2: Role of HBx protein in HBVreplication. Studies are proposed to determine the molecular basis for HBx activation of HBV reverse transcription and DNA replication. Model systems have been developed for delivery of hepadnavirus genomes to differentiated hepatocytic cell lines and rodent primary hepatocytes in culture, that permit viral replication in an HBx-dependent manner. Studies will investigate the role of HBx in viral replication in a biologically relevant system, focusing on HBx induction of HBV core protein phosphorylation, control of the cell cycle, and induction of nucleotide metabolism. HBx-dependent HBV replication will also be studied in primary hepatocytes prepared from mice that are deficient in genes that impact on HBV replication, including knockouts of Src and Pyk2 kinases, to better understand their importance for viral replication.