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

丙型肝炎病毒(丙型肝炎病毒)通常会造成终生感染，通常会导致严重的肝病和死亡。目前的药物治疗费用昂贵，效果不佳。我们的研究旨在描述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的特征。丙型肝炎病毒的一个特点是，它从一种称为多蛋白的单一大蛋白中产生病毒复制所需的所有不同蛋白。这是由病毒和细胞蛋白酶完成的，这是一种特殊的蛋白质，将多蛋白切割成单独的部分。我们开始了解其中许多病毒蛋白的作用，其中大多数对丙型肝炎病毒的复制是必不可少的。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，它们具有什么功能。我们还在研究不同的丙型肝炎病毒株在切割病毒多蛋白的方式上是否存在细微的差异。这可能为为什么一些菌株比其他菌株对当前的抗病毒治疗更具抵抗力提供了解释。

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.