Regulating viral protein production and stability using small molecules

病毒是非常有选择性和有效的核酸递送装置，其用作研究复杂蛋白质组装以及核心细胞功能的极好模型系统。一些最复杂和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的情况下，单纯疱疹病毒2型，病毒是由大约100种不同的蛋白质构建的。班菲尔德实验室的研究重点是了解这些迷人结构组装的机制。 虽然在研究病毒组装方面已经取得了很大进展，但这一进展受到了许多病毒组分对于成功生产新病毒体至关重要的事实的阻碍。在本申请中，我们探索了调节病毒蛋白表达和稳定性的新方法，以解决与当代程序相关的问题。为此，我们将联合收割机结合使用尖端的遗传工具来操纵疱疹病毒基因组和两种新描述的方法来药理学调节蛋白质的生产。总之，我们建议通过开发专门设计用于克服当前最先进方法的固有局限性的新技术来解决病毒组装中以前难以解决的问题。如果我们的方法是成功的，预计我们的研究将产生深远的影响，不仅研究人员的能力，研究的动力学和调节病毒体组装和蛋白质功能，但也将提供额外的工具，用于分析其他多蛋白复合物中发现的动物细胞。

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.