CELL ENTRY AND SPREAD BY POLYOMA VIRUS

多瘤病毒进入细胞并传播

• 批准号: 6286540
• 负责人: THOMAS Livingston BENJAMIN
• 金额: $ 41.21万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6286540
• 关键词: Polyomavirus; X ray crystallography; electron microscopy; fluorescence microscopy; gene mutation; green fluorescent proteins; host organism interaction; intracellular transport; laboratory mouse; nuclear membrane; receptor binding; vascular endothelium; virus genetics; virus infection mechanism; virus protein; virus receptors; virus related neoplasm /cancer; virus replication

The overall goal of this project is a better understanding of the mechanisms of cell entry and spread by polyoma virus. This virus infects and transforms rodent cells in culture. When inoculated into newborn mice, it spreads rapidly and induces a wide array of tumors. The pathway and mechanisms by which the virus infects cells will be studied in culture using electron microscopy and deconvolution fluorescence microscopy along with various immunological and biochemical methods. Specific aims are directed to identifying the mode of internalization, and the pathway of entry into the nucleus. Mutant viruses with defects in the structural proteins that affect entry will be characterized. We have identified an inbred mouse strain which is highly resistant to polyoma infection. The genetic and physiological bases for this host resistance will be investigated in crosses with susceptible mice, and by use of cell cultures derived from the resistant mice. The final goal of this line of investigation is the identification and understanding of the mode of action of the host resistance gene which blocks virus spread. We will also attempt to isolate polyoma virus from wild house mice and confirm the presence or absence of those determinants identified in laboratory strains which confer pathogenic properties to the virus.

本项目的总体目标是更好地了解 多瘤病毒进入细胞和传播的机制。这种病毒感染， 转化培养中的啮齿动物细胞。当接种到新生小鼠体内时， 迅速扩散并诱发多种肿瘤。途径和机制 病毒感染细胞的方式将在培养中使用电子显微镜进行研究。 显微镜和去卷积荧光显微镜沿着与各种 免疫学和生物化学方法。具体目标是 确定内部化的模式和进入内部化的途径， 原子核突变病毒的结构蛋白有缺陷， 入口将被标记。 我们已经鉴定出一种对多瘤病毒具有高度抗性的近交系小鼠品系 感染这种宿主抗性的遗传和生理基础将是 在与易感小鼠的杂交中以及通过使用细胞培养物进行研究 来自耐药小鼠。这次调查的最终目的 是识别和理解宿主的作用模式 阻止病毒传播的抗性基因。我们还将尝试分离 多瘤病毒从野生家鼠，并确认存在或不存在的那些 在实验室菌株中鉴定出的致病性 病毒的属性。