ROLE OF NUCLEIC ACID IN RNA VIRUSES

描述（来自申请人摘要的逐字描述）：病毒颗粒执行一个 在病毒复制周期中的一些基本功能。它们提供 一种稳定的容器，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，以生物活性的方式释放基因组， form.这些功能被有效地执行，并且具有高精度提升 现代病毒学的核心问题： 分子水平？病毒衣壳执行其功能的能力是 编码在其组成部分的化学和物理性质中。在这 应用我们计划集中在核酸在病毒装配中的作用， 其对病毒粒子的结构和功能特性的影响。本 最后，我们将使用高度发达的实验模型系统， 含有二十面体RNA的诺达病毒。病毒基因组传统上 被认为是相对被动的组件，除非他们从事 反映其作为遗传信息载体的作用的过程，例如， 转录和复制。越来越多的证据表明， 假设并不反映现实，至少在某些病毒中， 酸在通常与以下有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取得的成果 表明包装的nod病毒基因组限制了 病毒体及其被异源RNA替换导致畸变 在病毒组装过程中。这些观察结果表明，外壳蛋白和病毒 RNA建立了一个功能对话，在整个生命周期中保持 病毒粒子的。理解这一对话并认识到其更广泛的 这不仅对病毒研究具有内在的重要性， 为成功追求涉及病毒的实际应用， 粒子在这项建议中，我们将继续充分利用 Nodaviral模型系统提供的独特机会。在实验中 下面概述，我们打算阐明最初的分子细节， 外壳蛋白和RNA之间的相互作用，研究它们的相互依赖性 这两个组件在组装和分析如何外壳蛋白-RNA 相互作用表现在组装的物理性质中， 粒子这些研究的结果一般应适用于 医学上重要的正链RNA病毒。

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.