Membrane traffic pathways in viral replication and pathogenesis

"我们研究与艾滋病有关的人类免疫缺陷病毒（HIV），据信全世界有6000万人感染了这种病毒。在感染过程中，这些病毒必须与靶细胞表面表达的受体蛋白相互作用。利用这些受体的天然结合蛋白，有可能消除HIV感染。我们正试图了解这种调节的细胞和分子机制，目的是开发新的策略来下调受体。这些策略可能对艾滋病毒有效。重要的是，HIV利用的受体代表了一大类类似的蛋白质，即所谓的G蛋白偶联受体（GPCR），它们控制着包括免疫系统在内的一系列生物功能。因此，我们对HIV受体的了解可能与其他重要的生物学事件有关。||除了了解病毒进入，我们还研究了感染细胞内新病毒颗粒形成的分子和细胞机制。这就要求组成病毒颗粒的关键结构蛋白同时被买来，并放置在受感染的细胞内，这样病毒颗粒就可以形成。我们已经确定了包膜糖蛋白中的分子信号，这些信号是感染细胞内正确运输所必需的。当这些信号之一在猿猴模型系统中发生突变时，病毒就会减弱，不再具有致病性。此外，用该病毒处理的动物被保护免受正常致病性病毒的攻击。这些研究共同为发病机制提供了新的见解，并可能为免疫控制的关键组成部分提供提示。"

"We study the human immunodeficiency virus (HIV) that is linked to AIDS and is believed to have infected 60 million people worldwide. During infection these viruses must interact with receptor proteins expressed on the surfaces of target cells. Using the natural binding proteins of these receptors, it is possible to abrogate HIV infection. We are trying to understand the cellular and molecular mechanisms that underlie this regulation with the aim of developing novel strategies to down regulate the receptors. Such strategies may have efficacy against HIV. Importantly, the receptors exploited by HIV are representative of a large class of similar proteins, so-called G protein coupled receptors (GPCRs), that control a range of biological functions including the immune system. So what we learn about HIV receptors may have relevance to other important biological events.||In addition to understanding virus entry, we also investigate the molecular and cellular mechanisms involved in the formation of new virus particles within infected cells. This requires that the key structural proteins that make up virus particles are bought together at the same time and place within an infected cell so that virus particles can form. We have identified molecular signals in the envelope glycoprotein that are required for the correct trafficking within infected cells. When one of these signals is mutated in a simian model system, the virus is attenuated and is no longer pathogenic. Moreover, animals treated with this virus are protected against challenge with normal pathogenic viruses. Together these studies are providing novel insights to the mechanisms of pathogenesis and may give hints to the key components of immune control."