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

点击翻译按钮获取中文摘要

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.