PAPILLOMAVIRUS

本项目的总体目标是了解如何 乳头瘤病毒复制它们的基因组。 乳头瘤病毒在 近年来出现了非常重要的致病因素，在人类 疾病这些病毒，作为其正常生命周期的一部分， 转化上皮细胞引起良性肿瘤， 低但显著的频率可变成恶性的。 更深 了解病毒的一般生命周期和DNA复制 特别是，对于理解 疾病，它的传播，并最终为发展 有效的治疗措施。 我们正在研究 使用体内和无细胞两种方法研究乳头瘤病毒的特性 复制系统。我们将这些研究与遗传学和 病毒蛋白和序列元件的生化分析， 是病毒DNA复制所必需的 在这个项目中，我们将 继续我们对乳头瘤病毒复制子的一般描述 重点介绍了病毒E1和E2的特殊功能 病毒DNA复制中的蛋白质。 我们建议（一）研究 E2转录因子的结构和功能， 病毒DNA复制所需的;（ii）研究结构和 病毒起始蛋白E1蛋白的功能， 以及这两种蛋白质如何相互作用;（iii） 确定如何，作为这种相互作用的结果，一个复制能力 形成引发剂络合物;和（iv）研究引发剂络合物的参与。 稳定质粒维持中的E1和E2蛋白。 这些研究 将进一步加深我们对乳头状瘤病毒 启动并控制复制。 此外，互动 E1和E2蛋白之间的联系呈现出有趣的潜力， 药物干预的目标，这些研究将大大 增进我们对这种相互作用的了解。

The overall goal of this project is to understand how papillomaviruses replicate their genomes. Papillomaviruses have in recent years emerged as very important causal agents in human disease. These viruses, as a part of their normal life cycle, infect and transform cells in the epithelium causing benign tumors that with a low, but significant, frequency can become malignant. A deeper understanding of the viral life cycle in general, and DNA replication in particular, is of critical importance for the understanding of the disease, its transmission, and ultimately for the development of effective therapeutic measures. We are studying the replication properties of papillomaviruses using both in vivo and cell free replication systems. We are combining thee studies with genetic and biochemical analyses of the viral proteins and sequence elements that are required for viral DNA replication. In this project we will continue our general characterization of the papillomavirus replicon with emphasis on the specific functions of the viral E1 and E2 proteins in viral DNA replication. We propose (I) to study the structure and function of the E2 transcription factor which is required for viral DNA replication; (ii) to study the structure and function of the E1 protein which is the viral initiator protein, and also how these two proteins interact with each other; (iii) to determine how, as a result of this interaction, a replication competent initiator complex is formed; and (iv) to study the involvement of the E1 and E2 proteins in stable plasmid maintenance. These studies will further our general understanding of how papillomavirus replication is initiated and controlled. In addition, the interaction between the E1 and E2 proteins presents an interesting potential target for drug intervention and these studies will significantly advance our knowledge about this interaction.