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嗜神经的病原体， 将在体外用神经和非神经来源的细胞进行研究。 将比较宿主细胞受体对狂犬病病毒的特异性 神经毒力和无毒力狂犬病毒株， 具有相关嗜神经性的病毒。 直接证据表明狂犬病 病毒粒子“刺突”糖蛋白负责病毒粒子附着到 将从以下获得互补细胞受体单位（CRU）： 竞争性附着抑制实验。 最低限度的基本 病毒粒子附着蛋白（VAP）的结构需要附着到 将使用纯化的大尺寸聚集体研究CRU 天然“尖峰”和较小形式的VAP下降到糖肽片段 病毒粒子“刺突”糖蛋白的结构 VAP上的附着位点及其 构象结构将分别用单克隆抗体进行研究。 直接针对VAP的抗体和化学修饰的VAP 制备物作为阻断剂以抑制VAP附着于CRU。 抑制病毒粒子附着于易感细胞，这是由 直接抗小鼠细胞表面抗原的单克隆抗体 将进一步研究神经母细胞瘤细胞（抗“受体”活性） 用抗“受体”单克隆抗体评估细胞的存在， 未感染和狂犬病病毒感染细胞表面受体抗原。 目前可用的抗“受体”单克隆抗体和那些 将与可溶性受体成分一起产生，因为免疫原将提供 强大的工具来寻找类似的特异性受体 体内活性。 最后，可溶性VAP-CRU附着复合物将被 从细胞中分离以分析放射性标记的受体组分 从最初的附着开始参与病毒的结合 阶段并以病毒固定术结束。

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.