PAPILLOMAVIRUS

该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。乳头瘤病毒已经进入 近年来出现了非常重要的人类致病因素 疾病。这些病毒，作为其正常生命周期的一部分，感染和 转化上皮细胞，导致良性肿瘤 虽然频率很低，但意义重大，可能会变得恶性。更深一层的 了解病毒的一般生命周期和DNA复制 尤其是对于理解 疾病，它的传播，并最终导致 有效的治疗措施。我们正在研究复制 人乳头瘤病毒体内和体外特性的研究 复制系统。我们正在将你的研究与遗传和 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(I)研究 E2转录因子的结构和功能 病毒DNA复制所需的；(Ii)研究其结构和 作为病毒启动蛋白的E1蛋白的功能，以及 以及这两种蛋白质如何相互作用；(Iii) 确定作为此交互作用的结果，复制能力如何 形成了引发剂复合体；以及(Iv)研究了 E_1和E_2蛋白在稳定质粒中的维持。这些研究 将进一步加深我们对乳头瘤病毒如何 复制是启动和控制的。此外，这种互动 在E1和E2蛋白之间呈现了一个有趣的潜力 药物干预的目标，这些研究将显著 增进我们对这种互动的了解。

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.