IDENTIFYING TARGETS FOR THERAPEUTIC INTERVENTIONS USING PROTEOMIC TECHNOLOGY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这是太平洋西北国家实验室的一项研究，旨在表征已知致病性的正痘病毒颗粒的综合蛋白质组。其中包括野生型非致病性牛痘病毒（VV; Western Reserve毒株）和致病性人猴痘病毒（MPV;扎伊尔毒株）。在这个目标中，将确定致病性MPV的细胞外包膜病毒（EEV）和细胞内成熟病毒（IMV）的蛋白组分，并与VV的蛋白组分进行比较。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颗粒是无包膜的，完全具有感染性，非常稳定，是病毒的最丰富形式，这使得它们非常适合用于武器化，因为它们非常适合传播感染。EEV颗粒具有包膜、感染性和较不稳定性，被认为介导病毒在体内的长距离传播。阐明两种感染性颗粒，IMV和EEV从致病性和非致病性分离株的总蛋白质组分，将导致新的见解，在正痘病毒形态发生，并将作为一个数据库，用于识别新的抗原疫苗开发或病毒靶点的创建小分子抑制剂。

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.