Cellular Entry Route for Viral and Bacterial Pathogens

病毒和细菌病原体的细胞进入途径

• 批准号: 7669795
• 负责人: TOMAS KIRCHHAUSEN
• 金额: $ 36.39万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-25 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7669795
• 关键词: Actins; Bacteria; Biochemistry; Biological Process; Cells; Cellular Structures; Clathrin; Culicidae; Dengue Virus; Destinations; Ebola virus; Endocytosis; Event; Filovirus; Flavivirus; Genetic; Image; Individual; Infection; Infectious Agent; Invaded; Life; Listeria; Mammalian Cell; Measurement; Mediating; Molecular; New England; Outcome; Particle Size; Pathway interactions; Pattern; Phagocytes; Process; Recruitment Activity; Reporter; Role; Route; Tacaribe Complex Viruses; Time; Tissues; Transferrin; Transferrin Receptor; Tropism; Vesicular stomatitis Indiana virus; Viral; Virion; Virus; West Nile virus; Work; antimicrobial; biodefense; cellular imaging; enteropathogenic Escherichia coli; env Gene Products; fluorescence imaging; inhibitor/antagonist; meetings; novel strategies; pathogen; receptor; research study; tool; trafficking; uptake

Viruses and many bacteria must invade a cell to replicate, and cell entry is a step usefully accessible to inhibitors. Studies of pathogen entry have advanced our understanding of basic cell biological processes and led to discovery of new molecular mechanisms, while also providing opportunities to consider novel strategies for intervention. During the last decade, approaches using biochemistry, genetics, and real-time imaging have led to identification of a number of alternative modes of pathogen uptake, with sometimes subtle, yet critical differences in the way particular cellular structures are deployed. Direct fluorescence imaging of individual internalization events, combined when appropriate with pharmacological or genetic perturbation, resolves ambiguities associated with "ensemble" measurements, and we rely on its use throughout this proposal. This project focuses on understanding the role of multiple modes of clathrin-mediated endocytosis for viral entry and how they relate to the destination of endocytosed virus, information that is relevant to strategies for inhibiting entry, to analysis of cell tropism and different outcomes for infection of different tissues, and to relating information from entry of pseudotyped viruses with heterologous envelope proteins to entry of authentic virions. This project also aims to understand the role of the clathrin endocytic machinery in infection by invasive and adherent bacterial pathogens.

病毒和许多细菌必须侵入细胞才能复制，而进入细胞是一个有用的步骤， 抑制剂的病原体进入的研究促进了我们对基本细胞生物学过程的理解， 导致发现新的分子机制，同时也提供了考虑新的 干预战略。在过去的十年中，使用生物化学，遗传学和实时 成像已经导致识别了许多病原体摄取的替代模式，有时 在特定细胞结构的部署方式上存在细微而关键的差异。直接荧光 个别内化事件的成像，适当时结合药理学或遗传学 扰动，解决了与“合奏”测量相关的模糊性，我们依赖于它的使用 在整个提案中。 该项目的重点是了解网格蛋白介导的内吞作用的多种模式的病毒， 进入以及它们如何与内吞病毒的目的地相关，与 抑制进入，分析细胞向性和不同组织感染的不同结果，以及 将来自具有异源包膜蛋白的假型病毒的进入的信息与来自具有异源包膜蛋白的假型病毒的进入的信息相关联。 真正的病毒体该项目还旨在了解网格蛋白内吞机制在 侵入性和粘附性细菌病原体感染。