A RECEPTOR MEDIATING CELL-CELL AND CELL-AIDS VIRUS INTERACTIONS

CD4与II类MHC的相互作用对于细胞免疫应答是必不可少的。 免疫应答，而CD4与HIV包膜的关联是 艾滋病病毒感染的关键步骤。 的理解 参与这两个矛盾过程的分子机制形成了 这一提议的基础。 实验描述定义的作用 CD4和CD8在伴随胸腺发育的选择事件中的作用。 将嵌合的CD4和CD8基因引入转基因小鼠中， 允许分析细胞内信号时产生的， 胸腺细胞参与I类MHC，以及这些信号在 II类分子的结合。 一系列独立的实验是 描述了检查CD4介导的精确分子事件， HIV与靶细胞的结合和进入。 证据 这表明靶细胞上的CD4以外的分子 可能需要促进有效的病毒进入。 我们希望隔离 编码这些因子的基因，以提供新的见解， HIV的进入机制超出了最初与CD4的联系。 这 也可能允许构建对HIV易感的转基因小鼠 感染 最后，CD4可能不是作为一个被动的附着位点， HIV，但可能在导致病毒的融合事件中起重要作用 入境 我们设计了一系列实验来研究CD4是否是 仅需要允许病毒在靶细胞中紧密贴壁 膜，或者CD4是否也在后结合中发挥重要作用， 促进HIV的融合和进入。 综合来看，这些基因 而生物化学实验最终可能允许解剖 导致HIV与细胞膜融合的分子事件。

The interaction of CD4 with class II MHC is essential for the cellular immune response, while the association of CD4 with the HIV envelope is an essential step in AIDS virus infection. An understanding of the molecular mechanisms involved in these two paradoxical processes form the basis for this proposal. Experiments are described to define the role of CD4 and CD8 in the selection events that accompany thymic development. The introduction of chimeric CD4 and CD8 genes into transgenic mice will permit an analysis of the intracellular signals generated when a thymocyte engages class I MHC, and how these signals differ upon engagement of class II molecules. A separate series of experiments are described to examine the precise molecular events by which CD4 mediates the association and entry of HIV with the target cell. Evidence is accumulating to suggest that molecules other than CD4 on the target cell may be required to facilitate efficient viral entry. We wish to isolate the genes encoding such factors in order to provide new insight into the mechanisms of entry of HIV beyond its initial association with CD4. This may also permit the construction of transgenic mice susceptible to HIV infection. Finally, CD4 may not serve as a passive attachment site for HIV, but may play an important role in the fusion events leading to virus entry. We have designed a series of experiments to ask whether CD4 is required solely to allow the close apposition of the virus in target cell membrane, or whether CD4 also plays an important role postbinding, facilitating the fusion and entry of HIV. Taken together, these genetic and biochemical experiments may ultimately permit a dissection of the molecular events leading to the fusion of HIV with the cell membrane.