Temporal and co-ordinated processing of the Hepatitis C virus polyprotein as an important determinant of viral fitness

丙型肝炎病毒多蛋白的时间和协调加工作为病毒适应性的重要决定因素

• 批准号: G0701215/1
• 负责人: Christopher McCormick
• 金额: $ 44.35万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0701215%2F1
• 关键词: Temporal; co; ordinated; processing; Hepatitis

Hepatitis C virus (HCV) typically sets up a life-long infection often leading to severe liver disease and death. Current drug treatments are expensive and do not work well. Our research aims to characterise unexplored components of the virus life cycle that might be suitable as new targets for drug development. A feature of HCV is that it produces all the different proteins needed for viral replication from one single large protein, referred to as a polyprotein. This is done by both viral and cellular proteases, special proteins that cleave the polyprotein into its individual parts.We are starting to understand the role many of these viral proteins have, most of which are essential for HCV replication. However, our research indicates that the intermediate products generated during the cleavage of the polyprotein are also required for viral replication to occur.The challenge now is to work out which are the important intermediates and what functions they have. We are also looking at whether subtle differences exist between different strains of HCV in the way that they cleave their viral polyprotein. This might provide an explanation as to why some strains are more resistant to current anti-viral therapy than others.

丙型肝炎病毒（HCV）通常会导致终身感染，通常会导致严重的肝脏疾病和死亡。目前的药物治疗价格昂贵，效果不佳。我们的研究旨在探索病毒生命周期中可能适合作为药物开发新靶点的未探索成分。HCV的一个特征是它从一个单一的大蛋白质（称为多蛋白）产生病毒复制所需的所有不同蛋白质。这是由病毒和细胞蛋白酶完成的，这些特殊的蛋白质将多蛋白切割成单个部分。我们开始了解这些病毒蛋白质的作用，其中大多数是HCV复制所必需的。然而，我们的研究表明，在多蛋白裂解过程中产生的中间产物也是病毒复制所必需的，现在的挑战是找出哪些是重要的中间产物以及它们具有哪些功能。我们也在研究不同的HCV病毒株在切割病毒多蛋白的方式上是否存在细微的差异。这可能解释了为什么某些菌株比其他菌株对当前的抗病毒治疗更具抵抗力。