IDENTIFYING TARGETS FOR THERAPEUTIC INTERVENTIONS USING PROTEOMIC TECHNOLOGY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这是与太平洋西北国家实验室签订的一项分包合同，以确定已知致病性的正痘病毒颗粒的综合蛋白质组。这些病毒将包括野生型非致病性牛痘病毒(VV；西部储备株)和致病性人类猴痘病毒(MPV；扎伊尔株)。在这一目的中，将测定细胞外被膜病毒(EEV)和细胞内成熟病毒(IMV)的致病MPV的蛋白质组分，并与VV进行比较。进行这些研究的基本原理是EEV颗粒在结构、抗原性和生物学上与IMV颗粒不同。IMV颗粒无包膜，完全具有传染性，极其稳定，是病毒最丰富的形式，这使它们成为武器装备的理想选择，因为它们非常适合传播感染。EEV颗粒有包膜，具有传染性，不太稳定，被认为是病毒在体内的长期传播媒介。阐明来自致病和非致病分离株的IMV和EEV这两种感染性颗粒的总蛋白成分，将为正痘病毒的形态发生提供新的见解，并将作为鉴定疫苗开发的新抗原或创建小分子抑制剂的病毒靶点的数据库。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a subcontract with Pacific Northwest National Laboratories to characterize the comprehensive proteome of defined orthopoxvirus particles of known pathogenicity. These will include wild-type nonpathogenic vaccinia virus (VV; Western Reserve strain) and pathogenic human monkeypox virus (MPV; Zaire strain). In this objective, the protein components of the extracellular enveloped virus (EEV) and intracellular mature virus (IMV) will be determined for pathogenic MPV, and compared to that of VV. The rationale for performing these studies is that EEV particles are structurally, antigenically and biologically distinct from IMV particles. IMV particles are non-enveloped, fully infectious, extremely stable, and are the most abundant form of the virus, which makes them ideal for weaponizing, as they are well-suited to transmit infection. EEV particles are enveloped, infectious, and less stable, and are thought to mediate the long-range dissemination of virus in vivo. Elucidation of the total protein component of the two infectious particles, IMV and EEV from pathogenic and nonpathogenic isolates, will lead to new insights in orthopoxvirus morphogenesis, and will serve as a database for the identification of novel antigens for vaccine development or viral targets for the creation of small molecule inhibitors.