Membrane Traffic Pathways in Viral Replication and Pathogenesis

无论是人的直接感染，还是对家畜、农作物或一般环境的影响，病毒感染都是人类的主要健康和经济负担。病毒需要细胞进行感染和复制。了解病毒进入细胞的各种方式，利用其复制的细胞机制并发挥其致病潜力，是干预这些过程的关键。我们的工作旨在了解人类免疫缺陷病毒(HIV)、与艾滋病相关的感染源以及虫媒病毒登革病毒和塞姆利基森林病毒的细胞生物学方面的方面。登革病毒和塞姆利基森林病毒是由蚊子传播的两个病毒家族的代表，目前是热带大范围流行的罪魁祸首。我们将重点了解一组细胞蛋白质如何阻止这些病毒进入细胞的特定事件，以期利用这些蛋白质作为天然的感染抑制物。同时，我们的目标是利用多年来获得的知识来确定广谱、小分子、虫媒病毒感染的抑制剂，这些药物可用于预防或在流行情况下使用。我们将继续目前在病毒组装方面的工作，使用新的方法来了解病毒形成的细胞生物学，特别是对艾滋病毒来说，病毒蛋白中关键信号的修改是如何影响病毒致病机理的，这是正确组装病毒所必需的。

Whether direct infections of man or infections that impact on domestic animals, crops or the environment in general, virus infections are a major health and economic burdens for mankind. Viruses require cells for infection and replication. Understanding the various ways in which viruses gain entry to cells, exploit cellular mechanisms for their replication and exert their pathogenic potential is key to intervening in these processes. Our work aims to understand aspects of the cell biology of human immunodeficiency viruses (HIV), the infectious agents associated with AIDS, and the arboviruses Dengue virus and Semliki Forest virus, representatives of two families of viruses transmitted by mosquitoes and currently responsible for wide-spread epidemics in the tropics. We will focus on understanding how a set of cellular proteins can prevent specific events in the entry of these viruses into cells, with a view to exploiting these proteins as natural inhibitors of infection. In parallel, we aim to use knowledge acquired over many years to identify broad-spectrum, small molecule, inhibitors of arbovirus infection that can be used as prophylactics or in epidemic situations. We will continue current work on virus assembly, using new methods to understand the cell biology of virus formation and, for HIV in particular, how modification of key signals in viral proteins, required for correct virus assembly, impact on viral pathogenesis.