MOLECULAR MECHANISMS OF HIV-1 INFECTION

为了了解艾滋病病毒的发病机制， 艾滋病的新疗法，我们一直在研究 参与HIV-1细胞附着和感染人类细胞。 研究 针对表征1）细胞表面蛋白聚糖的作用， 在HIV结合和细胞渗透中的作用，以及2） CD 4依赖性病毒感染。 这些研究的目的是了解 艾滋病毒如何进入人体细胞，并确定蛋白质（受体） 细胞介导这些事件。 1. 细胞表面蛋白多糖在HIV感染中的作用。 以下 HIV最初与CD 4受体结合，病毒包膜被认为与 在附着和融合过程中与其他细胞表面分子结合。 我们正在研究进入通道中的第二种分子 CD 4依赖型病毒感染 在HIV附着在CD 4上后，我们观察到 包膜GP 120与细胞表面硫酸肝素蛋白聚糖结合 通过被称为V3结构域的包膜的特定区域。 肝素 硫酸盐结合需要寡聚体上构象完整的位点， HIV包膜的形式，并稳定三分子感染前 在T细胞表面的复合物。 这种相互作用对病毒至关重要 进入和感染，对于T细胞的进入尤其重要 热带病毒，这些病毒被认为会导致艾滋病的快速发展。 2. HIV新受体的鉴定。 我们正在描述细胞 感染原代和T细胞所需的表面分子 嗜性HIV分离株。 我们目前正在生产免疫试剂 它能特异性地与这些HIV结合结构反应， 这些抗体在生化和功能上表征了 分子。 基因探针正在被开发以克隆编码 在病毒感染期间与HIV相互作用的分子。 识别 HIV感染的分子靶点对于评估和 开发新的艾滋病疗法和疫苗。

In order to understand the pathogenesis of HIV and to evaluate and develop new therapies for AIDS, we have been studying the molecular events involved in HIV-1 cell attachment and infection of human cells. Studies were directed at characterizing 1) the role of cell surface proteoglycans in HIV binding and cell penetration and 2) novel receptors necessary for CD4-dependent virus infection. The goal of these studies is to understand how HIV enters human cells and to identify the proteins (receptors) on cells which mediate these events. 1. Role of cell surface proteoglycans in HIV infection. Following initial HIV binding to the CD4 receptor, virus envelope is thought to bind to other cell surface molecules during the attachment and fusion process. We are characterizing a second molecule in this entry pathway necessary for CD4-dependent virus infection. After HIV attaches to CD4, we observe that the envelope gp120 binds to cell surface heparin sulfate proteoglycan through a specific region of the envelope called the V3 domain. Heparin sulfate binding requires a conformationally intact site on the oligomeric form of the HIV envelope and stabilizes a trimolecular preinfection complex on the T-cell surface. This interaction is critical for virus entry and infection and is especially important to the entry of the T-cell tropic viruses, those viruses thought to induce rapid progression to AIDS. 2. Identification of novel receptors for HIV. We are characterizing cell surface molecules which are required for infection of primary and T-cell tropic HIV isolates. We are currently generating immunological reagents which specifically react with these HIV binding structures and are using these antibodies to biochemically and functionally characterize these molecules. Genetic probes are being developed to clone genes encoding molecules which interact with HIV during virus infection. Identifying the molecular targets of HIV infection is important to evaluating and developing new therapeutics and vaccines for AIDS.