Regulating viral protein production and stability using small molecules

病毒是非常有选择性和高效的核酸递送装置，是研究复杂蛋白质组合和核心细胞功能的优秀模型系统。一些最复杂且知之甚少的病毒是疱疹病毒科的成员。在我们实验室研究的模型疱疹病毒-2型单纯疱疹病毒的情况下，病毒由大约100种不同的蛋白质组成。班菲尔德实验室的一个研究重点是了解这些迷人的结构组装的机制。 虽然在研究病毒组装方面取得了很大进展，但由于许多病毒组件对于成功生产新的病毒粒子是必不可少的，这一进展受到了阻碍。在这项应用中，我们探索了调节病毒蛋白表达和稳定性的新方法，以缓解与当代程序相关的问题。为此，我们将结合使用尖端遗传工具操纵疱疹病毒基因组和两种新描述的蛋白质生产的药理学调节方法。总而言之，我们建议通过开发专门为克服当前最先进方法的固有限制而设计的新技术来解决病毒组装中以前难以解决的问题。如果我们的方法成功，预计我们的研究不仅将对研究人员研究病毒粒子组装和蛋白质功能的动力学和调节的能力产生深远影响，而且还将为分析在动物细胞中发现的其他多蛋白复合体提供额外的工具。

Viruses are remarkably selective and efficient nucleic acid delivery devices that serve as excellent model systems for studying complex protein assemblies as well as core cellular functions. Some of the most complicated and poorly understood viruses are the members of the Herpesviridae. In the case of the model herpesvirus studied in our laboratory, herpes simplex virus type 2, the viruses are built from about 100 different proteins. A focus of research in the Banfield laboratory is to understand the mechanisms by which these fascinating structures assemble. While much progress has been made in studying virus assembly, this progress has been hampered by the fact that many virus components are essential for the successful production of new virions. In this application we explore new approaches for regulating viral protein expression and stability that alleviates problems associated with contemporary procedures. To do this, we will combine the use of cutting edge genetic tools for the manipulation of herpesvirus genomes and two newly described methodologies for the pharmacological regulation of protein production. In sum, we propose to address a previously intractable problem in virus assembly by developing new technologies designed specifically to overcome inherent limitations of current state-of-the-art methodologies. If our approach is successful it is anticipated that our studies will have a profound impact on not only the ability of researchers to study the kinetics and regulation of virion assembly and protein function but will also provide additional tools for the analysis of other multiprotein complexes found in animal cells.