The Replication Initiator Protein E1 and its Interaction with DNA

描述(申请人提供)：乳头瘤病毒是一大类密切相关的病毒，可引起宿主中的疣。由这一群体的人类病毒感染生殖道是病毒感染和癌症发展之间少数牢固确立的联系之一。牛乳头瘤病毒，BPV，已作为这一组的原型，特别是在病毒DNA复制方面，但它的相对简单也用于检查DNA复制的一般机制特征。通过这个系统，单个蛋白质通过其不同的寡聚体形式包含复制启动中的关键事件，这为详细研究这些事件提供了一个很好的机会。我们的目标是建立一个关于复制起源的E1组装的机械观点，并在原子水平上对六聚体解旋酶的一般工作原理有一个理解。此外，病毒DNA复制机制本身也是抗病毒治疗的明显目标。复制所需的病毒蛋白的高分辨率结构等详细信息将极大地促进抗病毒药物的开发和测试。相关性：生殖道感染人乳头瘤病毒是病毒感染和癌症发展之间少数牢固确立的联系之一。牛乳头瘤病毒，BPV，已经成为这一组的原型，特别是在病毒复制方面。由于DNA复制相对简单，我们的目标是从机制上了解启动病毒复制的事件，这也使我们能够理解DNA复制的关键特征。这种复制所需的病毒蛋白的详细信息可以作为抗病毒治疗的目标，这将极大地促进抗病毒药物的开发和测试。尽管最近在疫苗开发方面取得了重要进展，但这些进展可能对已经感染的人群无效。

DESCRIPTION (provided by applicant): Papillomaviruses are a large family of closely related viruses that give rise to warts in their hosts. Infection of the genital tract by the human viruses from this group represents one of the few firmly established links between viral infection and the development of cancer. The bovine papillomavirus, BPV, has served as a prototype for this group especially regarding viral DNA replication, but its relative simplicity serves also to examine mechanistic features of DNA replication in general. This system, whereby a single protein encompasses the key events in replication initiation through its different oligomeric forms, provides a great opportunity to examine these events in detail. Our goals are to build a mechanistic view of the assembly of E1 on the origin of replication and an understanding toward the workings of hexameric helicases in general at an atomic level. In addition, the viral DNA replication machinery itself represents an obvious target for antiviral therapy. Detailed information such as high-resolution structures of viral proteins required for replication will greatly facilitate the development and testing of antiviral agents. Relevance: infection of the genital tract by the human papillomaviruses represents one of the few firmly established links between viral infection and the development of cancer. The bovine papillomavirus, BPV, has served as a prototype for this group especially regarding viral replication. It also enables the understanding of key features in DNA replication in general due to its relative simplicity Our objective is to gain a mechanistic understanding of the events that initiate viral replication. This type of detailed information of viral proteins required for its replication and that can serve as targets for antiviral therapy, will greatly facilitate the development and testing of antiviral agents. Through there have been important recent advances in vaccine development, these may not be effective to a population that has already been infected.