Nucleic Acids programmable Protein Array Core for Pathogenic Human Viruses

用于人类致病病毒的核酸可编程蛋白质阵列核心

• 批准号: 7671941
• 负责人: Grant McFadden
• 金额: $ 11.26万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-15 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7671941
• 关键词: Address; Antiviral Agents; Chikungunya virus; Chimeric Proteins; Collaborations; Complex; Democratic Republic of the Congo; Dengue; Dengue Virus; Development; Disease; Drug Delivery Systems; Elements; Generations; Genome; Goals; Human; Human Virus; Immune response; Immune system; Interferons; Libraries; Mediating; Microarray Analysis; Molecular; Monkeypox virus; Nucleic Acids; Open Reading Frames; Pathogenesis; Pathway interactions; Pharmacotherapy; Plasmids; Primates; Property; Protein Array; Protein Binding; Protein Microchips; Proteins; Proteome; Proteomics; Research Personnel; Screening procedure; Serotyping; Signal Pathway; Syndrome; Technology; Tropism; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Viral; Viral Proteins; Virulence; Virus; Virus Diseases; West Nile virus; Zoonotic Infection; base; biodefense; cytokine; expression vector; human coronavirus; interest; man; member; novel; novel diagnostics; pathogen; programs; protein protein interaction; response

This core proposal is to exploit viral pathogen protein microarrays for the purpose of identifying novel hostvirus protein interacting partners that regulate virus-host species tropism, host innate immune response and mediate pathogenic zoonotic infections in man. We propose to utilize a newly developed technology, NAPPA (Nucleic Acid Programmable Protein Arrays), which is currently being developed at the Harvard Proteomic Facility for the human proteome. We are now completing the construction of the monkeypox virus (MPV) proteome array (strain Zaire), but will expand the repertoire of the microarrays to include other viral pathogens of interest to SERCEB and the RCE program: starting with, human coronaviruses, dengue and Chikungunya virus. The virus-specific protein microarrays will be used to screen for novel human-virus protein interactions, with emphasis initially on the human inflammasome pathway, the interferon (IFN) pathway, and tumor necrosis factor (TNF) signaling pathway members. Viral proteome microarrays also have utility for studying anti-viral immune responses, screening for novel viral drug targets, and developing novel diagnostic strategies. Through the use of this proteomic platform technology, we seek to address the hypothesis that there are specific protein-protein interactions between proteins from human viral pathogens and human antiviral elements that are critical for host species tropism and pathogenesis in primates and man. By identifying viral/host protein interactions that regulate tropism and disease virulence properties of these viruses, we seek to identify specific targets for the development of novel antiviral strategies, as well as to better define the regulators of viral-induced pathogenic syndromes, such as the virus-induced "cytokine storm" that is thought to underlie the pathogenesis associated with a variety of zoonotic viral diseases in man. This project is being pursued in collaboration with the Harvard Proteomics Facility (Director: Josh LaBaer), which is developing the NAPPA technology to create human and select bacterial pathogen protein microarrays.

本研究的核心是利用病毒病原蛋白质微阵列来鉴定新的宿主病毒 调节病毒-宿主物种嗜性、宿主先天免疫应答和 介导人类致病性人畜共患病感染。我们建议利用新开发的技术，NAPPA （核酸可编程蛋白质阵列），这是目前正在开发的哈佛蛋白质组 人类蛋白质组研究所。我们现在正在完成猴痘病毒（MPV）的构建 蛋白质组阵列（扎伊尔株），但将扩大微阵列的剧目，包括其他病毒 SERCEB和RCE计划感兴趣的病原体：首先是人类冠状病毒，登革热和 基孔肯雅病毒病毒特异性蛋白质芯片将用于筛选新型人类病毒 蛋白质的相互作用，最初强调人类炎症体途径，干扰素（IFN） 途径，和肿瘤坏死因子（TNF）信号传导途径成员。病毒蛋白质组微阵列还 用于研究抗病毒免疫应答，筛选新的病毒药物靶点， 新的诊断策略。通过使用这种蛋白质组学平台技术，我们寻求解决 假设来自人类病毒病原体的蛋白质之间存在特异性蛋白质-蛋白质相互作用 和对灵长类动物中宿主物种嗜性和致病性至关重要的人抗病毒元件， 伙计通过鉴定病毒/宿主蛋白质相互作用，调节嗜性和疾病的毒力特性， 这些病毒，我们寻求确定新的抗病毒策略发展的具体目标，以及 为了更好地定义病毒诱导的致病性综合征的调节因子，例如病毒诱导的“细胞因子 风暴”，这被认为是与各种人畜共患病毒性疾病相关的发病机制的基础， 伙计该项目正在与哈佛蛋白质组学研究中心（主任：Josh）合作进行 LaBaer），该公司正在开发NAPPA技术，以创造人类和选择细菌病原体蛋白 微阵列