Determine the Three-Dimensional Structure of Icosahedral Virus Genomes

描述（由申请人提供）：基因组是病毒的感染性材料，因此正确的包装、储存和拆卸对成功感染至关重要。然而，人们对病毒基因组的三维结构知之甚少。我们开发了一种方法来确定包装在球形（二十面体）衣壳内的病毒基因组的结构。该技术使用来自低温电子显微镜的图像，并允许基因组结构的三维重建。该方法适用于模拟图像数据，我们提出用卫星烟草花叶病毒（STMV）的图像进行测试，这是一个简单的模型系统。成功的三维重建依赖于对许多粒子图像进行平均，并且前提是三维基因组排列在粒子之间是一致的。我们希望将我们的研究扩展到小核糖核酸病毒，一个重要的人类病原体家族，使用脊髓灰质炎病毒作为我们的模型系统。我们假设单个病毒物种的基因组具有一致的3D结构。通过验证这一假设，我们建议测试小核糖核酸病毒基因组重建方法的可行性。公共卫生相关性：为了有效感染，病毒基因组必须在三维空间中正确排列。了解三维基因组结构将使我们更全面地了解病毒是如何引起疾病的，并可能为抗病毒治疗提供见解。

DESCRIPTION (provided by applicant): The genome is a virus' infectious material, thus proper packaging, storage, and disassembly are critical to successful infection. Yet, little is known about the three- dimensional structure of viral genomes. We developed a method for determining the structure of viral genomes that are packaged inside spherical (icosahedral) capsids. The technique uses images from cryogenic electron microscopy and allows three- dimensional reconstruction of the genome structure. The method works for simulated image data, and we propose to test the technique with images of satellite tobacco mosaic virus (STMV), a simple model system. Successful 3D reconstruction relies on averaging many particle images and the premise that the three-dimensional genome arrangement is consistent from particle-to-particle. We expect to extend our study to picornaviruses, a family of significant human pathogens, using poliovirus as our model system. We hypothesize that the genomes of individual viral species have a consistent 3D structure. By testing this hypothesis, we propose to test the feasibility of picornaviruses for our genome-reconstruction method. PUBLIC HEALTH RELEVANCE: For effective infection, a virus' genome must be arranged correctly in three dimensions. Understanding 3D genome architecture will give a fuller mechanistic picture of how viruses cause disease and may give insights into anti-viral therapies.