NON-NEUTRALIZING ANTIBODIES IN ACUTE PRIMARY HIV INFECTION

HIV-1特异性研究中常规检测方法的不足 抗体的特点是它们经常无法检测到与 补体激活和Fc受体结合可能影响病毒 体内复制。补体激活抗体增强 形成包被补体的HIV-1，以抵抗补体溶解和 与多种细胞类型的补体受体(CR)结合，包括 滤泡树突状细胞、单核细胞、巨噬细胞、B淋巴细胞和红色 血细胞。抗体包被的病毒可能进一步与单核细胞相互作用 巨噬细胞通过Fc受体(FCR)独立于补体。每个人 其中的活性可能由免疫球蛋白类和 亚类并可通过以下方式影响HIV-1在体内的复制：1)增加 病毒进入或进入后复制导致感染增强，2) 向其上几乎没有或几乎没有CD4抗原的细胞扩增趋向性 表面，3)在表面捕获补体调理病毒 滤泡树突状细胞和4)通过单核细胞清除病毒 吞噬系统。我们将研究补体的免疫机制 HIV-1与CR、FCR在急性期的激活及相互作用 感染作为一种独特的环境来探索它们的可能性 有助于病毒复制或清除。一种方法是 确定体内补体激活是否与 免疫学、病毒学和临床特征。更多的研究将 表征循环中的HIV-1免疫复合体的外观和意志 评估它们的生化含量和生物学特性是否 由血清学相关因素预测。IgA、Ig M和Ig G的生产将是 评估以确定它们出现的时间和病毒抗原 关于亚类，将进一步描述特异性/免疫球蛋白。 将使用患者评估抗体的补体激活情况 分离株和自体血清在定量免疫分析中的应用。感染- 增强将在检测补体- 抗体增强HIV-1感染的依赖和非独立机制。 这些研究将提供有关血清学相关性的重要信息。 预测与CR和FCR相互作用的HIV-1致病机制 抑制病毒传播或控制血浆病毒血症。

A shortcoming of conventional assays used for the study of HIV-1-specific antibodies is that they often fail to detect activities associated with complement activation and Fc receptor binding that could influence virus replication in vivo. Complement-activating antibodies enhance the formation of complement-coated HIV-1 that resists complement lysis and binds complement receptors (CR) on a variety of cell types, including follicular dendritic cells, monocytes, macrophages, B lymphocyte and red blood cells. Antibody-coated virus may further interact with monocytes and macrophages through Fc receptors (FcR) independently of complement. Each of theses activities may be regulated by the immunoglobulin class and subclass and could influence HIV-1 replication in vivo by; 1) increasing virus entry or post-entry replication leading to infection-enhancement, 2) expanding tropism to cells that have little or no CD4 antigen on their surface, 3) trapping complement-opsonized virus on the surface of follicular dendritic cells and 4) clearing virus through the mononuclear phagocytic system. We will study immunologic mechanisms of complement activation and interactions of HIV-1 with CR and FcR during acute primary infection as a unique setting in which to explore their possible contribution to virus replication or clearance. One approach will be to determine whether complement activation in vivo correlates with immunological, virological and clinical profiles. Additional studies will characterize the appearance of circulating HIV-1 immune complexes and will assess whether their biochemical content and biological properties are predicted by serologic correlates. IgA, IgM and IgG production will be assessed to determine their timing of appearance and virus antigen specificity/ IgG will be further delineated with respect to subclasses. Antibodies will be assessed for complement activation using patient isolates and autologous sera in quantitative immunoassays. Infection- enhancement will be evaluated in assays that detect both complement- dependent and -independent mechanisms of antibody-enhanced HIV-1 infection. These studies will provide critical information on serological correlates of HIV-1 pathogenesis that predict interactions with CR and FcR involved in wither virus spread or in control of plasma viremia.