Determine the Three-Dimensional Structure of Icosahedral Virus Genomes

确定二十面体病毒基因组的三维结构

• 批准号: 7752592
• 负责人: David Michael Belnap
• 金额: $ 18.46万
• 依托单位: BRIGHAM YOUNG UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7752592
• 关键词: Algorithms; Animals; Architecture; Bacteriophages; Biological Models; Capsid; Capsid Proteins; Cardiovirus; Cell model; Coxsackie Viruses; Cryoelectron Microscopy; Crystallography; Data; Dimensions; Disease; Echo Viruses; Electron Microscopy; Enterovirus; Family; Family Picornaviridae; Genome; Human; Human poliovirus; Image; Individual; Infection; Knowledge; Lead; Methods; Modeling; Molecular Models; Noise; Polioviruses; Procedures; Process; Publishing; RNA; RNA Viruses; Resolution; Rhinovirus; Roentgen Rays; Role; Signal Transduction; Simulate; Site; Solutions; Specific qualifier value; Structure; Tail; Techniques; Testing; Three-Dimensional Image; Tobacco mosaic satellite virus; Viral; Viral Genome; Viral Physiology; Virion; Virus; Virus Assembly; Work; X-Ray Crystallography; cryogenics; data modeling; ds-DNA; image reconstruction; insight; interest; link protein; molecular modeling; particle; pathogen; prevent; public health relevance; reconstruction; research study; three dimensional structure; three-dimensional modeling; tomography; viral RNA

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.

描述（由申请人提供）：基因组是病毒的感染性物质，因此正确的包装、储存和拆卸对于成功感染至关重要。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。该技术使用低温电子显微镜的图像，并允许三维重建基因组结构。该方法适用于模拟图像数据，我们建议测试技术与卫星烟草花叶病毒（STMV），一个简单的模型系统的图像。成功的3D重建依赖于平均许多粒子图像和三维基因组排列从粒子到粒子是一致的前提。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，我们提出了测试的可行性，我们的基因组重建方法的小核糖核酸病毒。公共卫生相关性：为了有效感染，病毒的基因组必须在三维空间中正确排列。了解3D基因组结构将为病毒如何引起疾病提供更全面的机制图，并可能为抗病毒治疗提供见解。