Nucleic Acids programmable Protein Array Core for Pathogenic Human Viruses

这一核心建议是利用病毒病原体蛋白微阵列来鉴定新的宿主病毒 蛋白质相互作用的伙伴，调节病毒-宿主物种趋向性，宿主先天免疫反应和 为人的致病性人畜共患疾病提供中介。我们建议利用一项新开发的技术，NAPPA (核酸可编程蛋白质阵列)，目前正在哈佛蛋白质组开发 人类蛋白质组的设施。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)，但将扩大微阵列的保留范围，以包括其他病毒 SERCEB和RCE计划感兴趣的病原体：从人类冠状病毒、登革热和 基孔肯雅病毒。病毒特异性蛋白质微阵列将用于筛选新型人类病毒 蛋白质相互作用，最初重点是人类炎症体途径，干扰素(干扰素) 以及肿瘤坏死因子(TNF)信号通路成员。病毒蛋白质组微阵列也 对研究抗病毒免疫反应、筛选新的病毒药物靶点和开发 新的诊断策略。通过使用这种蛋白质组平台技术，我们寻求解决 假设人类病毒病原体的蛋白质之间存在特定的蛋白质-蛋白质相互作用 和人类抗病毒成分，对寄主物种的趋向性和灵长类动物的发病至关重要 天哪。通过鉴定病毒/宿主蛋白的相互作用来调节嗜性和疾病毒力特性 这些病毒，我们试图确定特定的目标，以开发新的抗病毒策略，以及 为了更好地定义病毒诱导的致病综合征的调节因素，如病毒诱导的“细胞因子” 风暴被认为是与各种人畜共患病毒疾病有关的发病机制的基础 天哪。该项目正在与哈佛蛋白质组学设施(主任：乔什)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。

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.