Molecular Biology and Genetics of Human Tumor Viruses

项目摘要/摘要 大约15%的人类癌症是由病毒引起的。人类癌症的病毒病因学可以有实质性的 对其治疗和预防的影响。例如，许多由病毒引起的人类癌症都是通过病毒表达的。 编码产品，这是抗病毒和肿瘤特异性治疗的潜在靶点。此外，独一无二的 细胞基因和途径有助于病毒相关性癌症，其中许多目前正在研究中。 作为抗癌治疗的靶点。该计划项目拨款(PPG)有两个主要目标：使用分子 生物学和遗传学阐明人类肿瘤病毒的生命周期和转化并翻译 这一认识转化为确定特定抗病毒、抗肿瘤治疗的靶点。我们专注于 在三个不同的病毒家族中研究人类肿瘤病毒：乳头瘤病毒、爱泼斯坦-巴尔病毒和卡波西病毒 肉瘤病毒。这三个病毒家族共同导致了许多与病毒相关的人类癌症。 本申请要求行政补编提供5个月的过渡性资金，直到具有竞争力的 2024年初为更新提供资金是为了支持当前PPG中5个项目中的4个(漏掉的一个项目 项目2的项目负责人丹·勒布博士已经退休)。四个项目的目标 项目1)确定和表征导致人类乳头瘤病毒相关癌症的细胞基因和 调节病毒感染；项目3)研究相关疱疹病毒基因组的复制和遗传 使用新的方法进行活细胞成像的细胞类型；项目4)表征细胞和病毒因素， 调节EB病毒(EBV)从潜伏到溶解的病毒状态的转换；以及项目5)定义驱动因素 研究EB病毒相关的致癌机制，并开发治疗这些癌症和疾病的新方法 由疱疹病毒引起的。此PPG有三个核心，可提供A)管理、统计 和生物信息学，B)仪器、显微镜和组织学，以及C)病毒工程和生产。 这些核心将在这一无成本延期期间从机构支助中获得资金，如 求职信。

PROJECT SUMMARY/ABSTRACT Viruses cause approximately 15% of human cancers. A viral etiology to a human cancer can have substantive consequences on its treatment and prevention. For example, many virally-caused human cancers express virally encoded products, which are potential targets for anti-viral, tumor-specific therapies. In addition, unique sets of cellular genes and pathways contribute to virally-associated cancers, many of which are currently being pursued as targets for anti-cancer therapies. This program project grant (PPG) has two major objectives: to use molecular biology and genetics to elucidate the life cycles of and transformation by human tumor viruses and to translate this understanding into the identification of targets for specific anti-viral, anti-tumor therapies. We are focused on studying human tumor viruses in three different virus families: papillomaviruses, Epstein Barr Virus, and Kaposi Sarcoma Virus. Together, these three families of viruses cause many of the virally-associated human cancers. This request for an Administrative Supplement to provide 5 months of bridge funding, until the competitive renewal is funded in early 2024 is to support 4 of the 5 projects in the current PPG (the one project left out has been sunsetted because Dr. Dan Loeb, Project Leader for Project 2, has retired). The goals of the four projects are: Project 1) to identify and characterize cellular genes that drive human papillomavirus-associated cancer and modulate viral infection; Project 3) to study the replication and inheritance of herpesviral genomes in relevant cell types using novel approaches for live cell imaging; Project 4) to characterize cellular and viral factors that regulate the switch from the latent to lytic viral state of Epstein Barr virus (EBV); and Project 5) to define drivers of EBV- associated carcinogenesis and develop novel approaches for treating these cancers and diseases caused by herpesviruses. There are three cores to this PPG that provide expertise in A) administration, statistics and bioinformatics, B) instrumentation, microscopy and histology, and C) virus engineering and production. These cores will be funded during this no cost extension period from institutional support as indicated in the cover letter.