Structure of the HIV-1 Genome

该项目将生物医学科学中两个广泛重要的问题联系起来。第一，人类免疫缺陷 艾滋病病毒（HIV）每年感染500万人，导致约300万人死亡。的研究 HIV的结构生物学对针对该病毒的治疗药物策略做出了重大贡献。的 HIV RNA基因组直接参与逆转录病毒感染周期的几乎每一个方面，但仍然是一个复杂的基因组。 一个全面的HIV-1基因组结构图将使它成为HIV-1的一个重要组成部分。 更容易确定抗逆转录病毒药物的新靶点，并设计siRNA和其他反义方法。 其次，基本上所有的RNA只有在折叠成特定的二级结构后才能在生物学中发挥作用。 现有的RNA结构作图技术是费力的且容易出错的，并且产生不完整的RNA结构图。 RNA结构我们的实验室开发了一种新的RNA结构分析技术， 与传统方法相关的问题，并得到广泛的成功探索的支持， 工作我们将把RNA结构分析发展成一种成熟的技术， 今天的排序。我们试图利用这项技术来分析整个HIV-1 RNA的结构 基因组 我们将与艾滋病毒生物学和生物信息学专家合作，实现以下目标： 一种完整的、无缝的技术，用于定量分析长RNA的结构。我们将使这个 所有感兴趣的生物医学科学家都可以使用的技术。(2)使用我们的高通量RNA结构 利用图谱技术获得整个HIV-1 RNA基因组的定量结构信息。（三） 确定病毒生命周期不同阶段基因组RNA结构的差异。 这项工作可能会大大推进我们对人类免疫缺陷病毒如何 以及如何干扰艾滋病毒的功能。这项工作通过创造一种工具来实现这一目标-- 简单的RNA结构分析-可以被生物医学科学家广泛用于解决各种各样的问题。 对人类健康有影响的生物学问题。

This project links two broadly important problems in biomedical science. First, the human immunodeficiency virus (HIV)infects 5 million people annually and causes ~3 million deaths through AIDS. Studies of the structural biology of HIV have contributed significantly to therapeutic drug strategies against the virus. The HIV RNA genome is directly involved in almost every aspect of the retroviral infectivity cycle, but remains the least well understood component of HIV.A comprehensive structural map of the HIV-1 genome will make it easier to identify new targets for antiretroviral drugs and to design siRNA and other antisense approaches. Second, essentially all RNAs function in biology only after they fold into a specific secondary structure. Existing RNA structure mapping technologies are laborious and error prone and yield an incomplete view of RNA structure. Our laboratory has developed a new RNA structure analysis technology that solves the problems associated with traditional approaches and that is supported by extensive successful exploratory work. We will develop RNA structure analysis into a mature technology roughly as straightforward as DNA sequencing is today. We seek to use this technology to analyze the structure of an entire HIV-1 RNA genome. In collaboration with experts in HIV biology and in bioinformatics, we will tackle the following Aims: (1) Create a complete, seamless technology for quantitative analysis of the structure of long RNAs. We will make this technology accessible to all interested biomedical scientists. (2) Use our high throughput RNA structure mapping technology to obtain quantitative structural information for an entire HIV-1RNA genome. (3) Determine differences in the genomic RNA structure at different stages in the viral life cycle. This work is likely to advance significantly our understanding of how the human immunodeficiency virus works and thus how to interfere with HIV functioning. This work accomplishes this goal by creating a tool -- facile RNAstructure analysis - that can be broadly used by biomedical scientists to address diverse biological problems with consequences for human health.