Hepatitis C viral protein translation modulation

该研究计划的长期目标是研究丙型肝炎病毒（HCV）蛋白的翻译。作为病毒生命周期中的一个重要步骤，HCV蛋白的翻译主要由位于5 '非翻译区（5' UTR）的内部核糖体进入位点（IRES）控制。此外，3 'UTR和非结构蛋白-5A（NS 5A）已显示影响HCV蛋白翻译。我们已经证明，HCV NS 5A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Akt 3参与调节HCV蛋白翻译。因此，本提案的短期目标是进一步表征HCV NS 5A调节HCV蛋白翻译的分子机制。我们将检验HCV NS 5A蛋白通过与HCV 3 'UTR结合和通过Akt 3介导的信号转导途径抑制HCV蛋白翻译的假设。研究将侧重于三个目标。

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.