HCV Nonstructural Proteins and Host Protein Secretion

HCV 非结构蛋白和宿主蛋白分泌

• 批准号: 6460335
• 负责人: Kouacou V. KONAN
• 金额: $ 13.26万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6460335
• 关键词: Flaviviridae; biological models; cell component structure /function; confocal scanning microscopy; endoplasmic reticulum; gene expression; genetic translation; hepatitis C virus; host organism interaction; immunologic techniques; protein localization; protein transport; secretion; tissue /cell culture; video microscopy; virus cytopathogenic effect; virus protein; virus replication

Hepatitis C virus (HCV) is one of the leading causes of liver cancer worldwide. Studies on HCV replication have been hampered by the lack of a convenient animal model or a reliable tissue culture system to propagate the virus. Investigators have focused on expression of HCV genes for functional and structural studies Most of the HCV non- structural proteins examined so far have been localized to the endoplasmic reticulum (ER). It is assumed therefore that expression of HCV NS4A/B precursor proteins results in the swelling of ER-like compartments and inhibits protein traffic between ER and Golgi apparatus. Thus, it is likely that HCV/NS4A/B o=precursor proteins inhibit cellular secretory pathway and modify intracellular compartments to form viral RNA replication complexes. In this proposal, the nature of the swollen intracellular compartments and their relationship to the HCV NS4A/B precursor proteins will be investigated. The ability of other HCV non-structural proteins (NS2/3/4A, NS4B/5A, NS4B/5A, NS4A and NS5B) to inhibit protein traffic will also be examined. Using MHC class I molecules, the specificity of this inhibition by HCV proteins will be tested. Similar studies will be done with homologous proteins of BVDV, a flavivirus that can be conveniently and safely be grown in tissue culture. Information gained from these studies will be useful in the selection of inhibitors or pathogenesis.

丙型肝炎病毒（HCV）是全世界肝癌的主要原因之一。由于缺乏方便的动物模型或可靠的组织培养系统来传播病毒，HCV 复制的研究受到阻碍。研究人员将重点放在HCV基因的表达上以进行功能和结构研究。迄今为止检查的大多数HCV非结构蛋白都定位于内质网(ER)。因此推测HCV NS4A/B前体蛋白的表达导致ER样区室的肿胀并抑制ER和高尔基体之间的蛋白质运输。因此，HCV/NS4A/B o=前体蛋白很可能抑制细胞分泌途径并修饰细胞内区室以形成病毒RNA复制复合物。在该提案中，将研究肿胀的细胞内区室的性质及其与 HCV NS4A/B 前体蛋白的关系。还将检查其他 HCV 非结构蛋白（NS2/3/4A、NS4B/5A、NS4B/5A、NS4A 和 NS5B）抑制蛋白运输的能力。使用 MHC I 类分子，将测试 HCV 蛋白抑制的特异性。类似的研究将利用 BVDV 的同源蛋白进行，BVDV 是一种可以方便、安全地在组织培养物中生长的黄病毒。从这些研究中获得的信息将有助于选择抑制剂或发病机制。