Plasmid Replicons of Human Tumor Viruses

人类肿瘤病毒的质粒复制子

• 批准号: 7465913
• 负责人: WILLIAM M. SUGDEN
• 金额: $ 23.27万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7465913
• 关键词: B-Lymphocytes; Binding Sites; Bos taurus; Cattle; Cell Cycle; Cells; Characteristics; Condition; DNA; DNA Tumor Viruses; DNA biosynthesis; DNA chemical synthesis; Development; Disease; Elements; Endothelial Cells; Epithelial Cells; Funding; Genome; Genomics; Goals; Herpesviridae; Human; Human Genome; Human Herpesvirus 4; Human Herpesvirus 8; Human Papillomavirus; Human papillomavirus 16; Infection; Kaposi Sarcoma; Latent virus infection phase; Lesion; Licensing; Life; Lymphoma; Maintenance; Malignant Neoplasms; Measures; Methods; Numbers; Oncogenic Viruses; Plasmids; Premalignant; Rate; Replicon; Research; Role; Terminal Repeat Sequences; Therapeutic Intervention; Umbilical vein; Viral; Virus; Virus Replication; Work; cancer cell; daughter cell; effusion; keratinocyte; neoplastic; neoplastic cell; research study; tumor

We want to understand functions that are distinctive to human tumor viruses in pre-neoplastic lesions and in tumor cells. These functions are potential targets for specific anti-viral therapies to treat viral associated cancers. We (Drs. Lambert and Sugden) have studied the replication of EBV and HPV for as long as their plasmid replicons have been known and recently extended our work to include KSHV. The goals of our research have been to characterize in detail the synthesis and partitioning of these viral replicons both to understand them in general and to uncover their unique features as targets for anti-viral, anti-tumor therapies. During this funding period we have developed a method to visualize individually EBV's plasmid replicons in live cells throughout a cell cycle. This approach has revealed a non-random, efficient mechanism for EBV's partitioning and an intrinsic inefficiency in its DNA synthesis. We shall extend this approach to study the synthesis and partitioning of intact genomes of EBV, KSHV, and HPV16 in their natural host cells. In particular, we shall characterize the replication of EBV during the early steps of its infection of primary B-cells to identify its mechanism of establishment, examine the efficiencies of synthesis and partitioning of KSHV as a function of the number of its terminal repeats, and determine the efficiencies and modes of the synthesis and of partitioning of HPV16 in two kinds of epithelial cells. These experiments will help to define characteristics of the synthesis and partitioning of these human tumor viruses which are likely distinct from the human genome and thus potential targets for therapeutic intervention.

我们想要了解人类肿瘤病毒在肿瘤前病变和肿瘤中的独特功能。 肿瘤细胞。这些功能是治疗病毒相关疾病的特定抗病毒疗法的潜在靶点 癌症。我们（Lambert 博士和 Sugden 博士）长期以来一直在研究 EBV 和 HPV 的复制。 质粒复制子已为人所知，并且最近将我们的工作扩展到包括 KSHV。我们的目标 研究人员详细描述了这些病毒复制子的合成和分配 从总体上了解它们并揭示它们作为抗病毒、抗肿瘤靶标的独特功能 疗法。在此资助期间，我们开发了一种单独可视化 EBV 质粒的方法 整个细胞周期中活细胞中的复制子。这种方法揭示了一种非随机的、有效的 EBV 的分配机制及其 DNA 合成的内在低效率。我们将延长此 研究 EBV、KSHV 和 HPV16 完整基因组的合成和划分的方法 天然宿主细胞。特别是，我们将描述 EBV 在其早期阶段的复制过程。 感染原代 B 细胞以确定其建立机制，检查合成效率 并根据其末端重复次数对 KSHV 进行划分，并确定效率 以及HPV16在两种上皮细胞中的合成和分配模式。这些实验 将有助于确定这些人类肿瘤病毒的合成和分配特征 可能与人类基因组不同，因此是治疗干预的潜在目标。