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

全球预计有1.7亿人感染丙型肝炎病毒，并导致慢性肝病，导致肝硬变和肝细胞癌。病毒在受污染的血液中传播，并通过共用针头传播。该病毒具有很高的变异性；以前的感染似乎不能防止再次感染，生产疫苗的现实前景也不存在。延长药物治疗可以在一定比例的感染者中清除病毒，但治疗费用昂贵，而且有令人不快的副作用。为了制造新的和改进的治疗方法，我们需要更好地了解病毒是如何复制的。我们之前的研究已经确定了基因组的一个小区域，它对病毒复制的早期事件至关重要。它在这种可变病毒的所有分离株中都高度保守。我们有数据表明，这种元素形成了一个分子开关，控制着病毒生命周期中最早的两个事件？翻译病毒以制造蛋白质，以及病毒基因组的复制。我们建议继续进行这些研究，以明确这种开关是如何工作的，并在这样做的过程中，期望了解我们可以如何防止它被？从而阻止病毒的复制。

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.