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: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=571500
• 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. 1. Further characterize HCV 3'UTR binding and HCV protein translation modulation by NS5A. 2. Characterize how viral and cellular proteins modulate the effect of NS5A on HCV protein translation. 3. Study the impact of Akt3 on HCV protein translation modulation by HCV NS5A. This proposal will provide an excellent opportunity for the training of graduate students and undergraduate summer students in virology and molecular biology. The proposed research is very important because HCV is infecting up to 3% of the population. No vaccines are available and the efficacy of current anti-virals is far from satisfactory. Knowledge gained from this proposal may lead to new anti-viral development targeting HCV protein translation, NS5A RNA binding, NS5A phosphorylation, and/or Akt3. HCV has a homolog virus in domestic dogs (canine hepacivirus). HCV is also very similar to a bovine pathogen bovine viral diarrhea virus (BVDV). Therefore, this proposal will have important implications in the research of animal viruses.

该研究项目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步骤，HCV蛋白翻译主要受5‘非翻译区（5’UTR）内核糖体进入位点（IRES）控制。此外，3'UTR和非结构蛋白5a （NS5A）已被证明影响HCV蛋白翻译。我们已经证明HCV NS5A通过结合3'UTR中的poly-U/UC序列抑制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，本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。我们将验证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。