WOODCHUCK VIRUS--MOLECULAR BIOLOGICAL STUDIES

土拨鼠病毒——分子生物学研究

• 批准号: 3746505
• 负责人: R H MILLER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3746505
• 关键词: genetic mapping; genetic promoter element; hepatitis B virus group; liver neoplasms; neoplasm /cancer genetics; viral carcinogenesis; virus antigen; virus genetics; virus load; virus replication

The woodchuck hepatitis virus (WHV) is taxonomically and serologically related to the hepatitis B virus (HBV). Infection with each of these viruses is associated with acute and chronic hepatitis and hepatic cell carcinoma in their respective hosts and these associations appear to be etiological in nature. Thus, WHV infection of woodchucks provides a relevant and convenient model for understanding HBV infections of humans. Five major areas of study were pursued this year. First, we continued our investigations of the WHV X gene and found that this gene is very sensitive to alterations and is essential for viral replication in animal transfection experiments. Second, fine mapping of the X transcript promoter was used to identify the essential nucleotides in this cis- acting element. Third, we extended our previous experiments on the characterization of the bi-directional promoter of WHV. Fourth, progress was made in an attempt to identify a Mongolian marmot hepatitis virus. Fifth, two WHV isolates were shown to develop surface antigenemia and liver tumors at significantly different rates. The latter finding has important implications for understanding the molecular mechanisms involved in viral replication and in the oncogenic potential of hepadnaviruses. Thus, it is now possible to design experiments to understand the mechanism of hepadnavirus oncogenesis.

土拨鼠肝炎病毒（WHV）在分类学和血清学上是 与乙型肝炎病毒（HBV）有关。 感染其中每一种 病毒与急、慢性肝炎及肝细胞有关 各自宿主的癌症，这些关联似乎是 本质上是病因学。 因此，土拨鼠的 WHV 感染提供了 理解人类乙型肝炎病毒感染的相关且方便的模型。 今年开展了五个主要研究领域。 首先，我们继续 我们对 WHV X 基因的研究发现该基因非常 对改变敏感，对于动物体内的病毒复制至关重要 转染实验。 二、X转录本的精细作图 启动子用于识别该顺式中的必需核苷酸 作用元素。 第三，我们扩展了之前的实验 WHV 双向启动子的表征。 四、进展情况 旨在鉴定蒙古土拨鼠肝炎病毒。 第五，两种 WHV 分离株表现出表面抗原血症和 肝脏肿瘤的发生率显着不同。 后一个发现有 对于理解分子机制具有重要意义 参与病毒复制和致癌潜力 肝炎病毒。 因此，现在可以设计实验来 了解嗜肝DNA病毒致癌机制。