MOLECULAR MECHANISMS OF HIV-1 INFECTION

描述HIV-1在病毒感染过程中使用的分子途径 感染对于理解HIV的发病机制和 评估和开发艾滋病的新疗法和疫苗。 我们 一直在研究HIV-1细胞中涉及的早期分子事件， 附着和感染人体细胞。 我们正在调查：1） 细胞表面硫酸乙酰肝素蛋白多糖在嗜T细胞HIV中的作用 结合和细胞渗透，和2）分子事件介导 原发性/单核细胞嗜性病毒进入。 细胞表面蛋白聚糖的作用 艾滋病毒感染。 在最初的HIV与CD 4受体结合后， 病毒包膜被认为与其他细胞表面分子结合 在连接和融合过程中。 我们观察到乙酰肝素 硫酸蛋白聚糖（HS）介导病毒进入的一些第二步 通过与寡聚体形式的包膜gp 120相互作用， V3区的特定亚区或“主要中和” 域”。 这种相互作用控制病毒进入的动力学， 对病毒快速进入和感染至关重要。 HS合成的调节 这对于确定病毒通过这种方式进入的程度是很重要的。 通路 我们的研究结果还表明，其他分子与 V3区非常接近HS结合位点。 2. HIV共受体的鉴定。 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。 我们已经产生了针对细胞的单克隆抗体 能够生长原代病毒，并筛选这些抗体 来阻断艾滋病毒与HIV结合特异性反应的单克隆抗体 结构将进行生化和功能表征。 遗传 正在开发克隆编码分子的基因的方法， 介导原发性艾滋病毒感染。 识别HIV的分子靶点 感染对于理解和开发新的治疗方法是重要的 和艾滋病疫苗。

Characterizing the molecular pathways used by HIV-1 during virus infection is important to understanding both the pathogenesis of HIV and to evaluating and developing new therapies and vaccines for AIDS. We have been studying the early molecular events involved in HIV-1 cell attachment and infection of human cells. We are investigating: 1) the role of cell surface heparan sulfate proteoglycans in T cell tropic HIV binding and cell penetration, and 2) the molecular events mediating primary/monocytotropic virus entry.1. Role of cell surface proteoglycans in HIV infection. Following initial HIV binding to the CD4 receptor, the virus envelope is thought to bind to other cell surface molecules during the attachment and fusion process. We have observed that heparan sulfate proteoglycan(HS) mediates some the second steps in virus entry by interacting with an oligomeric form of envelope gp120 through a specific subregion of the the V3 region or "principal neutralizing domain". This interaction controls the kinetics of virus entry and is critical for rapid virus entry and infection. Regulation of HS synthesis is important for determining the extent of virus entry through this pathway. Our results also indicate that other molecules interact with the V3 region in close approximation to the HS binding site. 2. Identification of co-receptors for HIV. We are characterizing cell surface molecules which are required for infection of primary and T-cell tropic HIV isolates. We have generated monoclonal antibodies to cells competent to growth primary viruses and are screening these antibodies for HIV blocking activity. MAbs which specifically react with HIV binding structures will be biochemically and functionally characterized. Genetic approaches are being developed to clone genes encoding molecules which mediate primary HIV infection. Identifying the molecular targets of HIV infection is important to understanding and developing new therapeutics and vaccines for AIDS.