Biochemical analysis of papillomavirus replication

乳头瘤病毒复制的生化分析

• 批准号: 7555616
• 负责人: ARNE STENLUND
• 金额: $ 42万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7555616
• 关键词: Amino Acid Sequence; Benign; Binding Sites; Biochemical; Biochemical Process; Biological Assay; Biological Models; Bovine Papillomavirus; Complex; DNA Binding; DNA biosynthesis; Development; Disease; Elements; Epithelium; Event; Family; Frequencies; Genetic; Genome; Goals; Human Development; Human Virus; In Vitro; Life Cycle Stages; Link; Malignant - descriptor; Malignant Neoplasms; Measures; Molecular; Nuclear Extract; Oncogenic Viruses; Papillomavirus; Pathway interactions; Peptide Sequence Determination; Pharmacotherapy; Process; Program Research Project Grants; Property; Proteins; Replication Initiation; Replication Origin; Replicon; Research; Series; Structure; System; Therapeutic; Transcription Coactivator; Viral; Viral Proteins; Virus; Virus Diseases; cell transformation; genital infection; human disease; in vivo; member; prototype; public health relevance; transmission process; tumor; viral DNA

DESCRIPTION (provided by applicant): The overall goal of this proposal is to understand how papillomviruses replicate their genomes. Papillomaviruses have in recent years emerged as a very important causal agent in human disease. These viruses as 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 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 DNA replication of papillomaviruses in vivo and in vitro. We are combining genetic biochemical and structural analyses of the viral proteins and sequence elements that are required for viral DNA replication. In this proposal we will continue our in depth analysis of the papillomavirus replicon with emphasis on the assembly pathways responsible for the ordered recognition, distortion and unwinding of the viral origin of replication. We propose to (i) characterize the transition from the E12E22 complex to the E1 DT. (ii) To characterize the E1 DT and to analyze its transition to the DH. (iii) To investigate the properties of the E1 DH and to characterize its activity. (iv) To analyze nuclear extract activated E1 DH formation. PUBLIC HEALTH RELEVANCE: Papillomaviruses are very important causative agents of human disease. The viral DNA replication machinery presents one of the few potential targets for drug therapy. Our studies, which are directed towards understanding the viral DNA replication machinery in detail will provide new such potential targets.

描述（由申请人提供）：该提案的总体目标是了解乳头状病毒如何复制其基因组。近年来，乳头瘤病毒已成为人类疾病中非常重要的因果剂。这些病毒是其正常生命周期感染并转化上皮细胞的一部分，导致良性肿瘤的良性肿瘤可能会变得恶性。对总体而言，对生命周期的更深入了解，尤其是DNA复制，对于理解疾病，其传播以及最终的发展有效治疗措施至关重要。我们正在研究体内和体外的乳头瘤病毒的DNA复制。我们正在结合病毒DNA复制所需的病毒蛋白和序列元素的遗传生化和结构分析。在此提案中，我们将继续对乳头状病毒复制子的深入分析，重点是负责对复制病毒起源的有序识别，失真和放松的组装途径。我们建议（i）表征从E12E22复合物到E1 DT的过渡。 （ii）表征E1 DT并分析其过渡到DH。 （iii）研究E1 DH的特性并表征其活性。 （iv）分析核提取物激活了E1 DH的形成。公共卫生相关性：乳头瘤病毒是人类疾病的非常重要的病因。病毒DNA复制机制提出了药物治疗的少数潜在靶标之一。我们的研究旨在详细了解病毒DNA复制机制将提供新的潜在目标。