Role of HBx Protein in HBV Replication

描述(由申请人提供)：本计划的长期目标 了解乙肝病毒(乙肝病毒)HBx基因在病毒中的作用 感染。请注意，此赠款的标题已从 “转录和转化受乙肝病毒HBx蛋白”的作用 HBx蛋白在乙肝病毒复制中的作用“，以反映我们在 HBX。 目的1：人乙肝病毒HBx蛋白的分子机制 行动。HBx激活胞质信号转导通路。HBx激活 PYK2-Src酪氨酸激酶的信号通路代表了一个重要的 肝细胞系中病毒复制的活性。概述了研究概况 了解HBx激活Pyk2-Src信号的分子机制 转导，因为它与病毒的HBx刺激密切相关 复制。此外，HBX似乎拥有核功能，可能 刺激病毒转录。研究还将通过以下方式探讨其机制 HBx在病毒转录中的作用，包括可能在 细胞核，以及它对病毒复制的影响。 目的2：HBx蛋白在HBV复制中的作用。建议进行研究以确定 HBx激活乙肝病毒逆转录和DNA的分子基础 复制。已经开发了用于递送庚型核糖核酸病毒的模型系统 分化肝细胞系和啮齿动物原代肝细胞的基因组 在培养中，这允许病毒以HBx依赖的方式复制。研究 将研究HBx在病毒复制中的作用 相关系统，重点是HBx诱导乙肝病毒核心蛋白磷酸化， 控制细胞周期，并诱导核苷酸代谢。 依赖于HBx的乙肝病毒复制也将在原代肝细胞中进行研究 从缺乏影响乙肝病毒复制的基因的小鼠身上制备， 包括Src和Pyk2激酶的敲除，以更好地理解它们的 对病毒复制的重要性。

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.