STRUCTURE/FUNCTION OF THE PARAMYXOVIRUS HN PROTEIN

先前的工作表明，中和新城疫病毒(NDV) 通过一组针对其HN糖蛋白的单抗(MAb) 需要将单抗添加到四个具有不同功能的位置 抑制特性。长期目标是更好地理解 这一现象的基础及其与 中和多形性包膜病毒。 具体地说，该提案针对的是构建 新城疫病毒HN糖蛋白的“图谱”，与该分子的某些结构域有关 到特定的中和机制，可能到特定的位置 中和效率。这将通过决心来实现。 非中和抗原变异体HN的氨基酸序列 与糖蛋白上多个表位的单抗联合选择 与这些单抗中和病毒的机制研究(S) 传染性。这将使不同的机制相互关联成为可能。 以及与特定HN序列的中和效率。 其他目的包括表征持续存在的部分 未中和病毒及其与宿主细胞的相互作用。可能的 副粘病毒典型的多形性在病毒形成中的作用 将对持久性分数进行调查。此外，还可以通过 病毒-单抗与宿主细胞的复合体将与宿主细胞的复合体形成对比 未经治疗的病毒。 这些方法中的每一种都将解决现象的不同方面 这反过来将增加我们对以下机制的总体理解 中和这组病毒。

Previous work suggests that neutralization of Newcastle disease virus (NDV) by a panel of monoclonal antibodies (MAbs) specific for its HN glycoprotein requires the addition of MAbs to four sites having different functional inhibition properties. The long-term objective is a better understanding of the basis for this phenomenon and its relevance to the mechanism of neutralization of pleiomorphic enveloped viruses. Specifically, the proposal is aimed at the construction of "neutralization map" of the NDV HN glycoprotein, relating certain domains of the molecule to specific mechanisms of neutralization and possibly to site-specific efficiencies of neutralization. This will be accomplished by determination of the amino acid sequence of the HN of nonneutralizable antigenic variants selected with MAbs to several epitopes on the glycoprotein in conjunction with studies of the mechanism(s) by which these MAbs neutralize viral infectivity. This will make it possible to correlate different mechanisms and efficiencies of neutralization with specific HN sequences. Other aims include the characterization of the persistent fraction of nonneutralized virus and its interaction with the host cell. The possible role of the pleiomorphism typical of paramyxoviruses in the estasblishment of persistent fractions will be investigated. Also, the interaction of the virus-MAb complex with the host cell will be contrasted to that of the untreated virus. Each of these approaches will address a different aspect of the phenomenon which, in turn, will add to our overall understanding of the mechanism of neutralization of this group of viruses.