Biochemical, structural and functional analysis of a pseudoknot required for hepatitis C virus replication.

点击翻译按钮获取中文摘要

Hepatitis C virus infects a predicted 170 million people worldwide and causes chronic liver disease leading to cirrhosis and hepatocellular carcinoma. The virus is transmitted in contaminated blood and by needle-sharing. The virus is highly variable; prior infection does not appear to protect from re-infection and there is no realistic prospect of producing a vaccine. Extended drug treatment can clear the virus in a proportion of those infected, but treatment is expensive and has unpleasant side-effects. To make new and improved therapies we need to understand better how the virus replicates. Our previous studies have identified a small region of the genome that is critical for an early event in virus replication. It is highly conserved in all isolates of this variable virus. We have data to suggest that this element forms a molecular switch controlling two of the earliest events in the virus life cycle ? the translation of the virus to make proteins, and the replication of the virus genome. We propose to continue these studies to define exactly how this switch operates and, in doing so, expect to learn of ways in which we can prevent it from being ?tripped? and so halt the replication of the virus.