CELL MEMBRANE RECEPTORS FOR VIRUSES

狂犬病病毒的细胞受体，狂犬病病毒是一种严格的神经性病原体 活体将用神经和非神经来源的细胞进行体外研究。 将比较狂犬病病毒宿主细胞受体的特异性。 到神经毒力和无毒狂犬病毒株，最终 具有相关神经嗜性的病毒。直接证据表明狂犬病 病毒粒子“尖峰”糖蛋白负责将病毒粒子附着到 互补的细胞受体单位(CRU)将从 竞争性依恋抑制实验。最低要求 病毒粒子附着蛋白(VAP)的结构 CRU将使用大尺寸的纯化集合体进行研究 天然的“尖峰”和较小形式的VAP，直至糖肽片段 病毒粒子的“尖峰”糖蛋白。VAP上的附着站点及其 构象结构将用单克隆法单独研究 针对VAP的直接抗体和化学修饰的VAP 作为封闭试剂的制剂，以抑制VAP与CRU的附着。 抑制病毒粒子与敏感细胞的附着，这是由 直接抗小鼠细胞表面抗原的单抗 神经母细胞瘤细胞(抗“受体”活性)将被进一步研究。 用抗“受体”的单抗评价细胞的存在 未感染和狂犬病病毒感染的细胞表面受体抗原(S)。 目前已有的抗“受体”单抗和那些 将产生与免疫原将提供的可溶性受体成分 强大的工具，用于搜索可比的特定受体 活体内活动。最后，可溶性VAP-CRU附着复合体将被 从细胞中分离分析放射性标记受体组分 从最初的附着开始参与病毒的结合 阶段，并以病毒病结束。

Cellular receptors for rabies virus, a strictly neurotropic pathogen in vivo will be studied in vitro with cells of neural and non-neural origin. the specificity of the host cell receptor for rabies virus will be compared to that for neurovirulent and avirulent rabies strains and eventually to viruses with related neurotropisms. Direct evidence that the rabies virion"spike" glycoprotein is responsible for the attachment of virions to a complementary cellular receptor unit (CRU) will be obtained from competitive attachment inhibition experiments. The minimum essential structure of the virion attachment protein (VAP) required for attachment to the CRU will be investigated using a large size aggregate of purified native "spikes" and smaller forms of the VAP down to glycopeptide fragments of the virion "spike" glycoprotein. The attachment site on the VAP and its conformational structure will be investigated separately with monoclonal antibodies directly against the VAP and with chemically modified VAP preparations as blocking reagents to inhibit VAP attachment to CRUs. Inhibition of virion attachment to susceptible cells which is caused by monoclonal antibodies directly against cell surface antigens of mouse neuroblastoma cells (anti-"receptor" activity) will be further investigated with anti-"receptor" monoclonal antibodies to evaluate the presence of cell surfacr receptor antigen(s) on uninfected and rabies virus-infected cells. Anti-"receptor" monoclonal antibodies presently available and those which will be produced with soluble receptor components as immunogen will provide powerful tools with which to search for comparable specific receptor activity in vivo. Finally, soluble VAP-CRU attachment complexes will be isolated from cells to analyze the radiolabeled receptor components involved in the binding of virus beginning with the initial attachment stage and ending with viropexis.