COMPLEX INTERACTION BETWEEN AAV AND HPV

AAV 和 HPV 之间复杂的相互作用

• 批准号: 6373789
• 负责人: PAUL L HERMONAT
• 金额: $ 25.35万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6373789
• 关键词: RNase protection assay; adeno associated virus group; cell differentiation; cervix neoplasms; disease /disorder etiology; gene expression; genetic mapping; genetic transcription; helper virus; host organism interaction; human papillomavirus; human tissue; immunocytochemistry; microorganism interaction; northern blottings; tissue /cell culture; virion; virus replication

DESCRIPTION: (adapted from the investigator's abstract) Cervical cancer is the most common form of cancer in developing countries and the second most common cancer worldwide. Epidemiologically, human papillomaviruses (HPV) and adeno-associated viruses (AAV) are inversely associated with cervical cancer, with HPV "causing" (reviews 1-5) and AAV protecting against (6-14) this cancer. Our long-range goal is to understand the relationship and interactions between HPV and AAV and its impact on the process of cervical carcinogenesis. In seeking this goal, our first objective will be to investigate the mechanisms whereby HPV can support AAV productive replication, and how AAV negatively influences the natural history of HPV. The central hypothesis of this application is that AAV can interact in a complex manner, with both positive and negative aspects, on HPV s phenotypes (including DNA replication, transcription and oncogenesis), but that HPV gene expression is required for AAV productive replication and gene expression. Preliminary data presented here are fully consistent with this hypothesized bi-directional interaction. Their laboratories are well prepared to pursue the proposed specific aims as indicated by our publication records. Specifically we propose to: Aim #1: Determine if HPV can serve as a helper for AAV in a productive organotypic culture system ( raft ) for HPV, identifying the HPV genes responsible for the effect. Aim #2: Determine the affect of AAV infection on the HPV life cycle including: HPV DNA replication, HPV virion synthesis, HPV transcription, and host cell differentiation. HPV is a wide-spread sexually transmitted pathogen. The study of the AAV-HPV interaction is strongly needed because of likely alterations in HPVs pathogenesis in the presence of AAV. Furthermore, AAV-helper virus interactions are poorly understood. The AAV-HPV interaction provides a superior, simpler system for such studies. We expect to describe in an HPV helper virus system the kinetics and magnitude of AAV productive replication, and define the HPV genes responsible for this helper function. Furthermore, we expect to define the AAV MOI dependent effects on HPV s vegetative cycle and on the host tissue s differentiation program.

描述：（根据调查员的摘要改编）宫颈癌是 发展中国家最常见的癌症形式，第二大 全球常见的癌症。 在流行病学上，人乳头瘤病毒（HPV） 和腺相关病毒（AAV）与宫颈呈负相关 癌症，HPV“引起”（评论1-5）和AAV防止（6-14） 这个癌症。 我们的远程目标是了解关系和 HPV与AAV之间的相互作用及其对宫颈过程的影响 致癌作用。 在寻求这个目标时，我们的第一个目标是 研究HPV可以支持AAV生产力的机制 复制，以及AAV如何对HPV的自然历史产生负面影响。 该应用程序的中心假设是AAV可以在A中相互作用 在HPV的表型上具有正面和负面方面的复杂方式 （包括DNA复制，转录和肿瘤发生），但该HPV 基因表达是AAV生产性复制和基因所必需的 表达。 此处提供的初步数据与此完全一致 假设的双向相互作用。 他们的实验室很好 准备追求我们所提出的特定目标 出版记录。 具体来说，我们建议： 目的＃1：确定HPV是否可以作为生产力的AAV的助手 HPV的器官培养系统（RAFT），识别HPV基因 负责效果。 目标＃2：确定AAV感染对HPV生命周期的影响 包括：HPV DNA复制，HPV病毒体合成，HPV转录， 和宿主细胞分化。 HPV是一种广泛的性传播病原体。 研究 由于HPV的可能改变，因此强烈需要AAV-HPV相互作用 在AAV存在下发病机理。 此外，AAV-Helper病毒 互动知之甚少。 AAV-HPV相互作用提供了 卓越，更简单的研究系统。 我们希望在HPV中描述 助手病毒系统的动力学和AAV生产的大小 复制并定义负责此辅助功能的HPV基因。 此外，我们期望定义对HPV S的AAV MOI依赖性影响 营养循环和宿主组织的分化程序。

项目成果

The adeno-associated virus major regulatory protein Rep78-c-Jun-DNA motif complex modulates AP-1 activity.

腺相关病毒主要调节蛋白 Rep78-c-Jun-DNA 基序复合物调节 AP-1 活性。

• DOI: 10.1016/s0042-6822(03)00439-2
• 发表时间: 2003
• 期刊: Virology
• 影响因子: 3.7
• 作者: Prasad,CKrishna;Meyers,Craig;Zhan,De-Jin;You,Hong;Chiriva-Internati,Maurizio;Mehta,JawaharL;Liu,Yong;Hermonat,PaulL
• 通讯作者: Hermonat,PaulL