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

丙型肝炎病毒复制所需的假结的生化、结构和功能分析。

• 批准号: G0801197/1
• 负责人: David Evans
• 金额: $ 55.34万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0801197%2F1
• 关键词: Biochemical; structural; functional; analysis; pseudoknot

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.

丙型肝炎病毒感染全球预计有1.7亿人，并导致慢性肝病，导致肝硬化和肝细胞癌。病毒通过受污染的血液和共用针头传播。该病毒变异性很大，既往感染似乎不能防止再次感染，生产疫苗也没有现实的前景。延长药物治疗可以清除一部分感染者的病毒，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疗法，我们需要更好地了解病毒是如何复制的。我们以前的研究已经确定了基因组的一个小区域，这对病毒复制的早期事件至关重要。它在该变异病毒的所有分离株中高度保守。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。病毒翻译成蛋白质，以及病毒基因组的复制。我们建议继续进行这些研究，以确切地确定这种开关是如何运作的，并在这样做的时候，期望了解我们可以防止它的方法。绊倒了从而阻止病毒的复制。