Pox Proteomics

描述（由申请方提供）：本探索性研究项目的总体目标是对牛痘病毒（VV）病毒体进行蛋白质组学分析，这将为开发新的抗病毒干预策略和预防计划提供基础，以预防由正痘病毒（如天花）引起的疾病。自1990年以来，VV基因组已被测序（1），但大约一半的基因的作用仍然完全未知。尽管已经非常详细地研究了牛痘病毒的许多蛋白质，但是还没有对VV颗粒进行全面的蛋白质组学分析。为了促进我们对VV和正痘病毒家族其他致病性更强的成员的复制周期的理解，并发现可能成为新的抗病毒药物或新一代疫苗抗原的靶点的蛋白质，我们为该研究项目定义了两个具体目标：1.通过使用质谱建立细胞内成熟病毒（IMV）的病毒体特异性蛋白质组参考目录; 2.）对病毒体蛋白上存在的翻译后修饰（PTM）进行蛋白质组学分析，最初侧重于磷蛋白和酰基蛋白。预计VV的蛋白质组分析将产生新的病毒基因产物的表达和定位的信息。今后的工作可以集中于对它们的分离和深入定性。VV病毒体形式的全面蛋白质组参考图谱的可用性对于痘病毒学家来说将是无价的，并且将为病毒性疾病的新型预防和治疗策略提供关键数据。

DESCRIPTION (provided by applicant): The overall goal of this exploratory research project is to conduct a proteomic analysis of the vaccinia virus (VV) virion, which will provide the foundation for the development of new antiviral intervention strategy and prevention programs to prevent diseases caused by orthopoxviruses such as smallpox. The VV genome has been sequenced since 1990 (1), but the roles of about half of the genes have remained entirely unknown. Although, numerous proteins of vaccinia virus have been studied in great detail, there no comprehensive proteomic analysis of the VV particle is available. To advance our understanding of the replication cycle of the VV and other more pathogenic members of the orthopoxvirus family and to discover proteins that may become targets for a new antiviral drugs or antigens for a new generation of vaccines we define two specific aims for this research project: 1.) Establish virion-specific proteome reference catalogs for the intracellular mature virus (IMV) by using mass spectrometry; 2.) Perform proteomic analysis of post-translational modifications (PTMs) present on virion proteins, focusing initially on phosphoproteins and acylproteins. It is expected that the proteome analysis of VV will yield information on the expression and location of new viral gene products. Future efforts can then focus on their isolation and in-depth characterization. The availability of comprehensive proteome reference maps of the VV virion forms will be invaluable for poxvirologists and will provide key data for novel prevention and treatment strategies for viral diseases.