Hepatitis C viral protein translation modulation

丙型肝炎病毒蛋白翻译调节

• 批准号: 298484-2013
• 负责人: Liu, Qiang
• 金额: $ 2.62万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=594908
• 关键词: Hepatitis; viral; protein; translation; modulation

The long-term goal of this research program is to study hepatitis C virus (HCV) protein translation. As an important step in virus lifecycle, HCV protein translation is primarily controlled by an internal ribosomal entry site (IRES) present in the 5'untranslated region (5'UTR). In addition, 3'UTR and nonstructural protein-5A (NS5A) have been shown to impact HCV protein translation. We have demonstrated that HCV NS5A inhibits HCV protein translation through binding to the poly-U/UC sequence in the 3'UTR. In addition, our ongoing research showed that a cellular kinase Akt3 is involved in modulating HCV protein translation. As such, the short-term goal of this proposal is to further characterize the molecular mechanisms by which HCV NS5A modulates HCV protein translation. We will test the hypothesis that HCV NS5A protein inhibits HCV protein translation through binding to HCV 3'UTR and through Akt3-mediated signal transduction pathways. Research will focus in three objectives.

该研究计划的长期目标是研究丙型肝炎病毒（HCV）蛋白翻译。作为病毒生命周期的重要一步，HCV 蛋白翻译主要由 5' 非翻译区 (5'UTR) 中的内部核糖体进入位点 (IRES) 控制。此外，3'UTR 和非结构蛋白 5A (NS5A) 已被证明会影响 HCV 蛋白翻译。我们已经证明HCV NS5A 通过与3'UTR 中的poly-U/UC 序列结合来抑制HCV 蛋白翻译。此外，我们正在进行的研究表明，细胞激酶 Akt3 参与调节 HCV 蛋白翻译。因此，该提案的短期目标是进一步表征 HCV NS5A 调节 HCV 蛋白翻译的分子机制。我们将检验 HCV NS5A 蛋白通过与 HCV 3'UTR 结合并通过 Akt3 介导的信号转导途径抑制 HCV 蛋白翻译的假设。研究将集中在三个目标上。