Structural Protein Networks ("Interactome") in Herpesviruses

疱疹病毒中的结构蛋白网络（“Interactome”）

• 批准号: 7268146
• 负责人: Heng Zhu
• 金额: $ 23.89万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7268146
• 关键词: Affect; Antiviral Agents; Biological; Biology; Capsid; Clinical; Complex; Cytomegalovirus; DNA Packaging; Data; Development; Electrons; Elements; Family; Future; Genetic; Genome; Glycoproteins; Goals; Herpes Labialis; Herpesviridae; Herpesvirus 1; Human; Human Herpesvirus 4; Human Herpesvirus 7; Human Herpesvirus 8; Infection; Intervention; Investigation; Keratitis; Lead; Life; Malignant Neoplasms; Mediating; Membrane; Methodology; Methods; Morphogenesis; Mutation; Nuclear; Phenotype; Phosphorylation; Phosphotransferases; Process; Protein C; Protein Kinase; Protein Microchips; Proteins; Public Health; Range; Role; Simplexvirus; Structural Protein; Structure; System; Tail; Viral; Virion; Virus; Virus Assembly; Work; ds-DNA; innovation; insight; novel; numb protein; particle; pathogen; polypeptide; viron

DESCRIPTION (provided by applicant): The herpesvirus virion is comprised of four structural elements: a large double-stranded DNA molecule in the central core; an icosahedral capsid, which encloses the genome; a layer that immediately surrounds the capsid termed the tegument; and an outer membrane or envelope, which encloses the whole structure and in which are embedded the viral glycoproteins. The assembly and maturation of the infectious particle is a complex and poorly characterized process. The goal of this project is to elucidate the process of virion assembly in herpesviruses using a newly developed protein chip approach. Our working hypothesis is that virus assembly and maturation is a sequential process and is dependent on ordered interactions between multi-protein complexes. We will focus on analyzing protein interactions among 23 conserved structural proteins from each of alphaherpesvirus (HSV-1), betaherpesvirus (HCMV and HHV-7), and gammaherpesvirus (KSHV and EBV) families as well as two additional proteins specific for HSV-1, a total of 117 structural proteins. We will construct herpesvirus protein chips containing the 117 proteins and apply an innovative approach for identifying protein interactions at multiple levels. Further, we plan to identify the specific substrates of the conserved herpesvirus-encoded protein kinase (UL13, ORF36, BGLF4, UL97, and U69) as well as those of the alphaherpesvirus conserved protein kinase US3 using the above protein chips, and determine to what extent the phosphorylation of the identified substrates will affect their abilities to interact with other proteins/protein complexes. The integration of all the data will allow us to build a complex protein interaction network that will provide insights into the sequence and order of the virion assembly in herpesviruses. Herpesviruses are major human pathogens that cause life-long persistent infections and result in clinical manifestations that range from a mild cold sore, to ocular keratitis and even cancer. Thus, infections due to these viruses are a major public health concern and understanding the biology of herpesviruses is important in the development of efficacious treatments of these infections. The major practical significance that will result from the above studies is the identification of essential interactions that can be used to develop virus- specific antivirals.

描述（由申请人提供）：疱疹病毒病毒由四个结构元素组成：中心核心中的大型双链DNA分子；一个包围基因组的二十面体capsid；立即围绕着tegument的衣壳的层；以及外膜或包膜，它封闭了整个结构，并嵌入病毒糖蛋白。传染粒子的组装和成熟是一个复杂且表征较差的过程。该项目的目的是使用新开发的蛋白质芯片方法在疱疹病毒中阐明病毒体组件的过程。我们的工作假设是病毒组装和成熟是一个顺序过程，并且取决于多蛋白质复合物之间的有序相互作用。我们将重点介绍分析来自αHerpesvirus（HSV-1），β-Herpaherpesvirus（HCMV和HHV-7）的23种保守结构蛋白的蛋白质相互作用，以及gammaherpesvirus（kshv and eBV）家族的gammaherpesvirus（KSHV和EBV），以及对HSV-1的另外两个蛋白质的特定于HSV-1的蛋白质。我们将构建包含117蛋白的疱疹病毒蛋白芯片，并采用创新方法来识别多个水平的蛋白质相互作用。此外，我们计划确定保守疱疹病毒编码的蛋白激酶（UL13，ORF36，BGLF4，UL97和U69）的特定底物，以及αHERPESVIRUS保守的蛋白质激酶US3的特定蛋白激酶，并使用上述蛋白质Chips和确定的差异来影响其相互作用的蛋白质激酶US3蛋白质/蛋白质复合物。所有数据的集成将使我们能够构建一个复杂的蛋白质相互作用网络，该网络将提供有关疱疹病毒中病毒体组件序列和顺序的见解。疱疹病毒是引起终生持续感染的主要人类病原体，并导致临床表现，从轻度酸痛到眼部角膜炎甚至癌症。因此，由于这些病毒引起的感染是一个主要的公共卫生关注，并且了解疱疹病毒的生物学在开发这些感染的有效治疗方面很重要。上述研究将产生的主要实际意义是鉴定可用于开发病毒抗病人的基本相互作用。