Elucidating the mechansim by which viruses manipulate cellular signalling pathways

阐明病毒操纵细胞信号传导途径的机制

• 批准号: 326829-2006
• 负责人: Ingham, Robert
• 金额: $ 0.79万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=397433
• 关键词: Elucidating; mechansim; viruses; manipulate; cellular

In order for a virus to mount a successful infection, it must utilize the host-cell machinery to gain entry into the cell, initiate viral replication, and evade the host immune response.  Viruses have evolved a number of means of dealing with these problems, and one of my research interests is understanding how, at the molecular level, viruses interact with the host cell.  Currently, my focus is directed towards how the Epstein-Barr virus (EBV) protein, Latent Membrane Protein 2A (LMP2A), manipulates cellular signalling pathways to influence cellular behavior, and ultimately, how this benefits the virus. LMP2A contains a number of short protein-protein interaction motifs that enable it to recruit cellular signalling proteins.  Through recruiting these signalling proteins, LMP2A can in some cases inhibit, and in others mimic, host cell signalling pathways.  This is critically important for the virus, as manipulating cellular signalling pathways allows EBV to remain undetected and persist in the body and likely provides a survival advantage to the EBV-infected cell.  My aim is to understand, using a variety of biochemical and molecular techniques, how LMP2A manipulates cell signalling pathways and modifies cellular behavior to the advantage of the virus.

为了使病毒获得成功的感染，它必须利用宿主细胞机制进入细胞，启动病毒复制，并逃避宿主免疫反应。这些病毒已经进化出许多处理这些问题的方法，我的研究兴趣之一是在分子水平上了解病毒如何与宿主细胞相互作用。目前，我的重点是EB病毒(EBV)蛋白，潜伏膜蛋白2A(LMP2A)如何操纵细胞信号通路，影响细胞行为，并最终如何使病毒受益。LMP2A包含许多短的蛋白质-蛋白质相互作用基序，使其能够招募细胞信号蛋白。通过招募这些信号蛋白，LMP2A在某些情况下可以抑制宿主细胞信号通路，在另一些情况下可以模仿宿主细胞信号通路。这对病毒至关重要，因为操纵细胞信号通路使EBV保持不被检测并在体内持续存在，并可能为EBV感染的细胞提供生存优势。我的目的是了解LMP2A如何操纵细胞信号通路并改变细胞行为，以利于病毒。