Cis- and Trans-acting Factors in HCV Gene Expression

HCV 基因表达中的顺式和反式作用因子

• 批准号: 7146715
• 负责人: Shelton Stewart Bradrick
• 金额: $ 5.04万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7146715
• 关键词: 3' Untranslated Regions; Accounting; Affect; Affinity; Antiviral Therapy; Biological Assay; Cells; Characteristics; Chronic; Cirrhosis; Communication; Complex; Family; Gene Expression; Genetic Translation; Genome; Genomics; Hepatitis C; Hepatitis C virus; Hepatocyte; Histocompatibility Testing; Indium; Life Cycle Stages; Liver; Liver Failure; Liver diseases; Mediating; Molecular; Morbidity - disease rate; Phase; Play; Polypyrimidine Tract-Binding Protein; Polyribosomes; Primary carcinoma of the liver cells; Process; Protein Biosynthesis; Proteins; RNA; RNA Viruses; RNA chemical synthesis; RNA replication; Rate; Replicon; Reporter; Research; Role; Site; Specificity; Staging; System; Testing; Trans-Activators; Translation Initiation; Translations; Tropism; Untranslated Regions; Viral; Virus Replication; base; density; in vivo; insight; mortality; novel; research study; viral RNA

Hepatitis C virus (HCV) is a major world-wide cause of chronic liver disease and hepatic failure for which effective therapies are needed. Within the positive-strand RNA genome of HCV exists an internal ribosomal entry site (IRES) that mediates viral gene expression. Significant efforts have been directed toward characterization of HCV IRES-mediated translation initiation, partly because the HCV IRES presents an attractive target for antiviral therapy. However, a role for specific c^-acting HCV RNA elements in translation control and the function of trans-acting cellular proteins in this process remains obscure. This proposal examines the molecular mechanism of translation initiation at the HCV IRES and its modulationby the 3' nontranslatedregion, the polypyrimidine tract binding protein, and previously unidentified trans-acting factors. Cis- and trans-acting regulatory factors will be characterized through the utilization of a novel cell- based reporter expression system that takes into account the complex involvement of viral and cellular determinants in translationcontrol at the HCV IRES.

丙型肝炎病毒（HCV）是慢性肝病和肝衰竭的主要原因 需要有效的疗法。 HCV的阳性RNA基因组内存在内部核糖体 介导病毒基因表达的进入位点（IRE）。大量的努力已指向 HCV IRES介导的翻译启动的表征，部分是因为HCV IRES呈现 抗病毒治疗的有吸引力的靶标。但是，在特定的c^acting HCV RNA元素中的作用 在此过程中，翻译控制和跨作用细胞蛋白的功能仍然晦涩难懂。这 提案检查了HCV IRES及其调制的分子转换启动的分子机制 3'非翻译区域，息肉嘧啶道结合蛋白和以前未识别的反式作用 因素。通过利用新细胞 - 基于基于的记者表达系统，该系统考虑了病毒和细胞的复杂参与 HCV IRES的TranslationControl中的决定因素。