CELL MEMBRANE RECEPTORS FOR VIRUSES

狂犬病病毒与细胞表面早期相互作用的继续研究 受体将集中在细胞受体的化学性质上 培养细胞及该受体探针的研制 体外研究结果与狂犬病病毒在体内附着的相关性。 我们之前的研究表明狂犬病病毒附着在细胞表面 本质上可能是脂类的成分。因此，我们将调查狂犬病 病毒附着在不同结构特征的糖脂上 动物起源。我们将确定该病毒的生物学特异性 病毒-糖脂相互作用的脂质体包含不同 附着性和感染性抑制试验中的糖脂。 狂犬病病毒感染培养物中的pH依赖性细胞-细胞融合 将通过研究酸诱导的构象变化来研究细胞 狂犬病病毒糖蛋白中。针对以下目标的单抗 病毒糖蛋白将通过以下方式定位构象变化区域 比较抗原性分析。此外，酸处理的病毒糖蛋白将 与未经处理的糖蛋白结合的特异性进行比较 中性糖脂暗示病毒的“第二结合部位” 与吸附内吞作用有关的糖蛋白。 我们将继续开发用于体内的可溶性受体探针。这些 将包括代表构象图像的抗独特型抗体 对单个糖蛋白表位和放射性标记病毒进行观察 病毒在各种组织的冰冻切片中的分布。我们会 确定狂犬病病毒与分离的乙酰胆碱的关系 直接结合和结合竞争分析中的受体使用一组 针对乙酰胆碱受体复合体的单抗。 最后，我们将尝试定位狂犬病病毒上的离散区域 与糖蛋白结合的单价糖蛋白 (Fab)抗糖蛋白单抗片段。这些研究 旨在使用结构来理解病毒趋向性的本质 以嗜神经性病原体狂犬病病毒为模型。

The continued study of early interactions of rabies virus for cell surface receptors will focus on the chemical nature of the cellular receptor on cultured cells and the development of probes of this receptor to study the relevance of in vitro findings to the attachment of rabies virus in vivo. Our previous studies suggested that rabies virus attaches to a cell surface component which may be lipid in nature. Thus, we will investigate rabies virus attachment to various structurally characterized glycolipids of animal origin. We will determine the biologic specificity of virus-glycolipid interactions using liposomes containing the various glycolipids in attachment and infectivity inhibition assays. The pH dependent cell-cell fusion in cultures of rabies virus-infected cells will be studied by investigating acid-induced conformational change in the rabies virus glycoprotein. Monoclonal antibodies directed toward the viral glycoprotein will locate regions of conformational change by comparative antigenic analysis. Also, acid-treated viral glycoprotein will be compared to untreated glycoprotein for the specificity of binding to neutral glycolipids suggesting a 'second binding site' of the virus glycoprotein related to adsorptive endocytosis. We will continue to develop soluble receptor probes for use in vivo. These will include anti-idiotypic antibodies, representing conformational images of individual glycoprotein epitopes, and radiolabeled virus to observe virus distribution in cryostat sections of various tissues. We will determine the relationship between rabies virus and isolated acetylcholine receptor in direct binding and binding competition assays using a panel of monoclonal antibodies directed against the acetylcholine receptor complex. Finally, we will attempt to localize discrete areas on the rabies virus glycoprotein responsible for attachment and fusion by using monovalent (Fab) fragments of anti-glycoprotein monoclonal antibodies. These studies are aimed at understanding the nature of viral tropism using the struct neurotropic pathogen, rabies virus, as a model.