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Characterization of the reovirus simga 1s protien.

呼肠弧病毒 simga 1s 蛋白的表征。

基本信息

批准号：
7485441
负责人：
Karl W Boehme
金额：
$ 4.96万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7485441
关键词：
Animals Apoptosis Biological Assay Cell Cycle Cell Cycle Arrest Cell Cycle Progression Cell Cycle Proteins Cell physiology Cells Complement Complementary DNA Cultured Cells Development Disease Double Stranded RNA Virus Double-Stranded RNA Ectopic Expression Experimental Models Foundations Genes Genetic Genome Goals Growth Immunity Immunologics Induction of Apoptosis Infection Injury Kinetics Laboratories Lead Malignant Neoplasms Maps Mediating Molecular Mus Neuraxis Newborn Infant Nonstructural Protein Open Reading Frames Pathogenesis Pattern Peripheral Phosphorylation Plasmids Play Process Proteins Proteomics Reoviridae Infections Reovirus Research Role Route Serotyping Site Study models System Testing Viral Viral Pathogenesis Virus Virus Replication activator 1 protein base career defined contribution in vivo insight mutant neoplastic novel strategies positional cloning research study

项目摘要

DESCRIPTION (provided by applicant): Understanding how viruses disrupt normal cellular processes has provided tremendous insights into molecular mechanisms that underlie host cell function. Infection by mammalian reovirus, a highly tractable model for studies of dsRNA virus replication and pathogenesis, profoundly alters host cell physiology leading to cell cycle arrest and induction of apoptosis, processes intricately involved in cancer, immunity, and development. The reovirus nonstructural protein, a1s, is implicated in perturbation of the cell cycle and induction of apoptosis. However, mechanisms by which a1s mediates these effects are not known. Using a newly developed, plasmid-based reverse genetics system for reovirus, viruses were generated that contain either the wild-type a1s-encoding S1 gene segment or an S1 gene segment in which the a1s translational start site has been altered to block a1s synthesis. Experiments described in this application will use these otherwise isogenic viruses to define the function of a1s in reovirus replication and pathogenesis and determine the role of a1s in reovirus-induced cell cycle arrest and apoptosis. Three specific aims are proposed. The first specific aim will define the function of a1s in reovirus replication in cultured cells and determine whether a1s contributes to reovirus-induced apoptosis. The second specific aim will determine the effects of a1s on cell cycle progression and use proteomic approaches to identify cellular proteins with which a1s interacts. The third specific aim will define the contribution of a1s to reovirus-induced pathogenesis in vivo. Collectively, these studies will provide new insights into mechanisms by which reovirus infection modulates the host cell cycle and induces apoptosis. The goal of the experiments described in this application is to determine the function of reovirus a1s protein in modulating cell cycle progression, apoptosis, and viral pathogenesis. Findings from these studies could lead to new insights into these highly-regulated, interrelated processes that play fundamental roles in development, immunity, and cancer. Such insights might lead to new treatments for degenerative, immunologic, or neoplastic diseases.

DESCRIPTION (provided by applicant): Understanding how viruses disrupt normal cellular processes has provided tremendous insights into molecular mechanisms that underlie host cell function.哺乳动物呼肠孤病毒是一种用于研究 dsRNA 病毒复制和发病机制的高度易处理的模型，其感染深刻地改变宿主细胞生理学，导致细胞周期停滞和诱导细胞凋亡，这些过程与癌症、免疫和发育错综复杂。呼肠孤病毒非结构蛋白 a1s 与细胞周期的扰动和细胞凋亡的诱导有关。然而，a1s 介导这些作用的机制尚不清楚。使用新开发的基于质粒的呼肠孤病毒反向遗传学系统，生成的病毒包含野生型 a1s 编码 S1 基因片段或其中 a1s 翻译起始位点已被改变以阻止 a1s 合成的 S1 基因片段。本申请中描述的实验将使用这些其他同基因病毒来定义a1s在呼肠孤病毒复制和发病机制中的功能，并确定a1s在呼肠孤病毒诱导的细胞周期停滞和细胞凋亡中的作用。提出了三个具体目标。第一个具体目标是确定 a1s 在培养细胞中呼肠孤病毒复制中的功能，并确定 a1s 是否有助于呼肠孤病毒诱导的细胞凋亡。第二个具体目标是确定 a1s 对细胞周期进程的影响，并使用蛋白质组学方法来鉴定与 a1s 相互作用的细胞蛋白。第三个具体目标将确定 a1s 对呼肠孤病毒诱导的体内发病机制的贡献。总的来说，这些研究将为呼肠孤病毒感染调节宿主细胞周期和诱导细胞凋亡的机制提供新的见解。本申请中描述的实验的目的是确定呼肠孤病毒a1s蛋白在调节细胞周期进程、细胞凋亡和病毒发病机制中的功能。这些研究的结果可能会给人们带来对这些高度调控、相互关联的过程的新见解，这些过程在发育、免疫和癌症中发挥着重要作用。这些见解可能会带来退行性、免疫或肿瘤疾病的新疗法。