TYPE 12 ADENOVIRUS TRANSFORMATION-DEFECTIVE MUTANTS

12 型腺病毒转化缺陷突变体

• 批准号: 3170823
• 负责人: JAMES F WILLIAMS
• 金额: $ 14.1万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-08-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3170823
• 关键词: Adenoviridae; defective virus; gene mutation; genetic manipulation; kidney cell; laboratory mouse; laboratory rat; monoclonal antibody; mutant; oncogenic virus; serotyping; tissue /cell culture; viral carcinogenesis; virus antigen; virus assembly; virus cytopathogenic effect; virus diseases; virus genetics; virus infection mechanism; virus protein; virus replication

The overall, long-term objective of this research program is to use genetic, immunological, and molecular approaches to define the functions that the various type 12 adenovirus (Ad12) E1A and E1B proteins play in transforming rat and mouse cells in vitro, and to understand the basis for the strong oncogenicity of this serotype and the very striking difference in viral oncogenicity between this serotype and non-oncogenic serotypes such as 2 and 5. We are also interested in determining the roles of these E1 gene products in regulating the progress of infection in permissive human cells. Our specific aims over the next five years are to: 1) Analyze the roles of the Ad12 E1b 54Kd protein in the early phase of productive infection in human cells, and in ocogenic transformation of rodent cells. 2) Extend phenotypic analysis of the Ad12 E1B 19Kd mutants with a view to determining the basis for their differential DNA degradation and transformation phenotypes and defining the role of this protein in productive infection and transformation. 3) Extend mutational analysis of the roles of Ad12 E1A gene product functions in productive infection of human cells and oncogenic transformation of rodent cells. 4) Prepare and characterize monoclonal antibodies specific for each of the various Ad12 E1A and E1B proteins.

该研究计划的总体长期目标是 使用遗传，免疫学和分子方法来定义 各种12型腺病毒（AD12）E1A和 E1b蛋白在体外转化大鼠和小鼠细胞中发挥作用，并且 了解强烈的致癌性的基础 血清型和病毒致癌性的差异很大 在这种血清型和非癌性血清型之间，例如2和 5。我们也有兴趣确定这些E1的作用 基因产物调节允许感染的进展 人类细胞。 我们未来五年的具体目标是：1） 在早期分析AD12 E1B 54KD蛋白的作用 人类细胞中生产性感染和呼吸症 啮齿动物细胞的转化。 2）扩展表型分析 AD12 E1B 19KD突变体，以确定基础 对于它们的差异DNA降解和转化 表型并定义该蛋白在生产力中的作用 感染和转化。 3）扩展对突变分析 AD12 E1A基因产物的作用在生产力中起作用 人类细胞的感染和啮齿动物的致癌转化 细胞。 4）准备和表征特定于单克隆抗体 对于各种AD12 E1A和E1B蛋白中的每一个。