Role of HBx Protein in HBV Replication

HBx 蛋白在 HBV 复制中的作用

• 批准号: 6584902
• 负责人: Robert Schneider
• 金额: $ 5.95万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6584902
• 关键词: biological signal transduction; calcium ion; hepatitis B; hepatitis B antigens; hepatitis B virus group; host organism interaction; laboratory mouse; mitochondria; protein tyrosine kinase; protooncogene; transcription factor; virus genetics; virus infection mechanism; virus protein; virus replication

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.

描述（由申请人提供）：该提案的长期目标 旨在了解乙型肝炎病毒 (HBV) HBx 基因在病毒感染中的作用 感染。请注意，该补助金的名称已更改为 “乙型肝炎病毒HBx蛋白的转录和转化”的作用 HBx 蛋白在 HBV 复制中的作用”，以反映我们的研究进展 HBx。 目标1：人乙型肝炎病毒（HBV）HBx蛋白的分子机制 行动。 HBx 激活细胞质信号转导途径。 HBx激活 Pyk2-Src 酪氨酸激酶信号通路的研究代表了一个重要的 肝细胞系中病毒复制的活性。研究概述 了解 HBx 激活 Pyk2-Src 信号的分子机制 转导，因为它与病毒的 HBx 刺激紧密相关 复制。此外，HBx 似乎具有可能的核功能 刺激病毒转录。研究还将通过以下方式调查其机制： HBx 在病毒转录中发挥作用，包括在 核及其对病毒复制的影响。 目标 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。已开发出用于传递嗜肝DNA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 在培养物中，允许病毒以 HBx 依赖性方式复制。研究 将研究 HBx 在病毒复制中的生物学作用 相关系统，重点关注HBx诱导HBV核心蛋白磷酸化， 细胞周期的控制和核苷酸代谢的诱导。 HBx 依赖性 HBV 复制也将在原代肝细胞中进行研究 由缺乏影响乙肝病毒复制基因的小鼠制备而成， 包括 Src 和 Pyk2 激酶的敲除，以更好地了解它们 对于病毒复制的重要性。