Structural Analysis of Virulence Determinants and Genomic DNA Packaging Constraints in a ssDNA Virus

单链 DNA 病毒毒力决定因素和基因组 DNA 包装限制的结构分析

• 批准号: 0212846
• 负责人: Mavis Agbandje-McKenna
• 金额: $ 43.44万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0212846&HistoricalAwards=false
• 关键词: Structural; Analysis; Virulence; Determinants; Genomic

Capsid proteins play many functional roles during the life cycle of viruses, including host cell recognition, specific encapsidation of genomic nucleic acid, and the formation of the essential interactions required for progeny virus capsid assembly and release. For the ssDNA Parvoviridae, the exact role of their capsid proteins in these processes requires further elucidation. Genetics studies have shown that interaction of the major parvoviral capsid protein, VP2, with host cell factors play a crucial role in tissue tropism and entry into the host cell. The methodologies of X-ray crystallography, biochemistry and virology will be utilized to study two closely related strains of minute virus of mice, MVMi (immunosuppressive strain) and MVMp (prototype strain) and their interactions with sialic acid, a component of their infectious receptor, to gain insights into mechanisms of specificity of capsid interactions in virulence determination. In addition, the X-ray structure of MVMi, in which approximately 30% of the ssDNA genome is ordered provides a unique model for defining molecular interactions between a viral capsid and its genome that ensure selective recognition and packaging. The aim is to identify a possible genomic signature that drives parvoviral DNA recognition and encapsidation. Research developments and achievements will be integrated with educational training of senior undergraduate and graduate students in the use of a multidisciplinary approach to study macromolecular interactions.

衣壳蛋白在病毒的生命周期中发挥着许多功能，包括宿主细胞识别、基因组核酸的特异性结合以及子代病毒衣壳组装和释放所需的必要相互作用的形成。对于ssDNA细小病毒科，其衣壳蛋白在这些过程中的确切作用需要进一步阐明。遗传学研究表明，细小病毒主要衣壳蛋白VP2与宿主细胞因子的相互作用在组织嗜性和进入宿主细胞中起着至关重要的作用。本研究将利用X射线晶体学、生物化学和病毒学的方法，研究两种密切相关的小鼠微小病毒株MVMi（免疫抑制株）和MVMp（原型株）及其与其感染性受体组分唾液酸的相互作用，以深入了解衣壳相互作用在毒力测定中的特异性机制。此外，MVMi的X射线结构，其中约30%的ssDNA基因组是有序的，提供了一个独特的模型，用于定义病毒衣壳与其基因组之间的分子相互作用，以确保选择性识别和包装。目的是确定一个可能的基因组签名，驱动细小病毒DNA识别和识别。研究发展和成就将与高年级本科生和研究生的教育培训相结合，采用多学科方法研究大分子相互作用。