A novel viral modifier of TNF family receptor signalling: Elucidation of mechanisms of action

在数百万年的时间里，病毒已经进化出了大量的策略，使它们能够破坏宿主反应的有效性。我们发现，这些病毒策略之一似乎旨在阻止一种重要的抗病毒因子的合成，称为肿瘤坏死因子。在这个项目中，我们的目标是找出病毒因子如何在相关分子的水平上阻断细胞内肿瘤坏死因子的产生。本项目的第二个方面涉及病毒因子作用于细胞类型和反应以操纵宿主反应的鉴定。我们的理由是，这些信息将提高我们的理解肿瘤坏死因子的生产是如何调节和这种类型的反应在病毒感染和生理学的意义，更普遍。这项研究的应用将有助于设计更好的药物，用于治疗肿瘤坏死因子产生对病理学有显著影响的许多疾病，如类风湿性关节炎和自身免疫。在某些情况下，选择性地打开肿瘤坏死因子可能是一种治疗优势，例如用于治疗感染或癌症。

Over millions of years, viruses have evolved a great number of strategies to allow them to subvert the effectiveness of the host response. We have discovered that one of these viral strategies seems designed to block the synthesis of an important anti-viral factor, called tumour necrosis factor. In this project, we aim to work out how the viral factor blocks tumour necrosis factor production inside the cell, at the level of the molecules involved. The second aspect of this project concerns the identification of the types of cells and responses which the viral factor acts upon to manipulate the host response. We reason that this information will improve our understanding of how tumour necrosis factor production is regulated and the significance of this type of response in virus infection and physiology, more generally. The application of this research will be to aid the design of better drugs for the treatment of many conditions where tumour necrosis factor production contributes significantly to pathology, eg rheumatoid arthritis and autoimmunity. In some conditions, it may be a therapeutic advantage to selectively turn on tumour necrosis factor, eg for treatment of infections or cancer.