MOLECULAR BIOLOGY OF NDV MEMBRANE PROTEINS

新城疫病毒(NDV)是新城疫病毒的重要模式，但难度较大 研究副粘病毒，如麻疹、腮腺炎和呼吸道合胞病毒 病毒。它也仍然是一种禽类病原体，经常产生 在世界各地的家禽群中发生毁灭性的流行性传染病。在这 建议我们利用突变体、反变型和单抗 探索新城疫病毒的三种膜蛋白(HN、F和M)；特别强调 将被放置在HN上。这些蛋白质具有多种功能，其中一些 其中一些已经明确定义，而其他一些则没有。我们会 尝试将蛋白质(S)分配给尚未完成的功能，并 定位功能区和单抗结合部位 分子。使用野生型新城疫病毒，我们将分段HN，鉴定 二硫键或糖基化的多肽和位置，以及序列 重要的多肽。比较AV-WT和突变蛋白，我们将定位 突变。我们将使用针对这些蛋白质的单抗 功能抑制和多肽结合研究定位功能 区域。我们还将使用单抗来探测突变的变化。 蛋白质结合部位，并在抗HN抗体的情况下，选择 在重要区域发生改变的定点突变体 传染性。随着F的突变体和抗体的出现，我们将 对F进行类似的研究。最后，我们将进行更多的研究 关于突变体和回复突变体，以确认D组突变体的分配 M蛋白。我们将调查以前未检测到的HN的处理 并检测HN在溶血和传染性方面的作用(S)。

Newcastle disease virus (NDV) is the model for important, but difficult to study paramyxoviruses like measles, mumps, and respiratory syncytial viruses. It also remains an avian pathogen which produces frequent devastating epizootics in poultry flocks throughout the world. In this proposal we utilize mutants and revertants and monoclonal antibodies to explore NDV's three membrane proteins (HN, F and M); particular emphasis will be placed on HN. These proteins have multiple functions, some of which have been clearly defined and others of which have not. We will attempt to assign protein(s) to functions where this hasn't been done and locate functional areas as well as monoclonal antibody binding sites on the molecules. Using wild type NDV, AV-WT, we will fragment HN, identify peptides and sites of disulfide bonds or glycosylation, and sequence important peptides. Comparing AV-WT and mutant proteins we will map mutations. We will use monoclonal antibodies to these proteins in functional inhibition and peptide binding studies to locate functional areas. We will also use monoclonal antibodies to probe changes in mutant protein binding sites, and in the case of anti-HN antibodies, to select site-specific mutants with alterations in regions important to infectivity. As mutants and antibodies to F become available, we will conduct similar studies on F. Finally, we will conduct additional studies on mutants and revertants to confirm the assignment of group D mutants to the M protein. We will probe previously undetected processing of the HN protein and examine HN's role(s) in hemolysis and infectivity.