ROLE OF NUCLEIC ACID IN RNA VIRUSES

核酸在 RNA 病毒中的作用

• 批准号: 6625101
• 负责人: Anette Schneemann
• 金额: $ 37.97万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6625101
• 关键词: RNA virus; capsid; cryoelectron microscopy; genetic mapping; intermolecular interaction; nucleic acid structure; virion; virus RNA; virus assembly

DESCRIPTION (Verbatim from Applicant's Abstract): Virus particles perform a number of essential functions during the viral replication cycle. they provide a stable container that protects the genome during transport form cell to cell, they recognize receptor molecules on the surface of suitable target cells, they penetrate cellular membranes and release the genome in a biologically active form. These functions are performed efficiently and with high precision raising a question central to modern virology: how are capsid functions regulated at the molecular level? The ability of viral capsids to perform their functions is encoded in the chemical and physical properties of their components. In this application we plan to focus on the role of nucleic acid in viral assembly and its impact on the structural and functional properties of the virion. To this end, we will use the highly developed experimental model system represented by the icosahedral RNA containing nodaviruses. Viral genomes have traditionally been considered to be relatively passive components unless they are engaged in processes that reflect their roles as carriers of genetic information, e.g., transcription and replication. There is increasing evidence, however, that this assumption does not reflect reality and that at least in some viruses nucleic acid plays a much more significant part in functions commonly associated with the capsid protein. Results that we obtained in the previous funding period indicate that the packaged nod viral genome restricts the dynamic properties of the virion and that its replacement with heterologous RNA leads to aberrations during viral assembly. These observations suggest that coat protein and viral RNA establish a functional dialogue that is maintained throughout the lifespan of the virion. Understanding this dialogue and recognizing its broader implications is not only of intrinsic importance to virus research but also required for the successful pursuit of practical applications involving virus particles. In this proposal we will continue to take full advantage of the unique opportunities afforded by the nodaviral model system. In the experiments outlined below we intend to elucidate the molecular details of the initial interactions between coat protein and RNA, investigate the mutual dependency of the two components during assembly and analyze how coat protein-RNA interactions manifest themselves in the physical properties of the assembled particle. Results from these studies should be applicable in general terms to medically important positive strand RNA viruses.

描述（逐字摘自申请人的摘要）：病毒颗粒执行 病毒复制周期中的许多基本功能。他们提供 一个稳定的容器，在细胞间运输过程中保护基因组， 它们识别合适靶细胞表面的受体分子， 穿透细胞膜并以具有生物活性的方式释放基因组 形式。这些功能执行效率高，精度高 现代病毒学的一个核心问题：衣壳功能是如何调节的 分子水平？病毒衣壳执行其功能的能力是 编码在其成分的化学和物理特性中。在这个 我们计划重点关注核酸在病毒组装中的作用以及 它对病毒粒子的结构和功能特性的影响。对此 最后，我们将使用以 含有诺达病毒的二十面体RNA。传统上，病毒基因组 被认为是相对被动的元件，除非它们参与 反映其作为遗传信息载体的作用的过程，例如， 转录和复制。然而，越来越多的证据表明，这 假设并不反映现实，至少在某些病毒核酸中 酸在通常与以下相关的功能中起着更重要的作用 衣壳蛋白。我们在上一个资助期间获得的结果 表明包装的点头病毒基因组限制了 病毒体及其被异源 RNA 取代会导致畸变 在病毒组装过程中。这些观察结果表明外壳蛋白和病毒 RNA 建立了在整个生命周期中维持的功能对话 病毒体的。理解这种对话并认识到其更广泛的意义 影响不仅对病毒研究具有内在重要性，而且 成功追求涉及病毒的实际应用所需的 颗粒。在本提案中，我们将继续充分利用 nodaviral 模型系统提供了独特的机会。在实验中 下面概述我们打算阐明初始的分子细节 外壳蛋白和RNA之间的相互作用，研究它们的相互依赖性 组装过程中的两个组件并分析如何包裹蛋白质-RNA 相互作用体现在组装体的物理特性中 粒子。这些研究的结果应该普遍适用于 医学上重要的正链RNA病毒。