STRUCTURE/FUNCTION OF THE PARAMYXOVIRUS HN PROTEIN

副粘病毒 HN 蛋白的结构/功能

• 批准号: 2607762
• 负责人: RONALD M IORIO
• 金额: $ 29.07万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2607762
• 关键词: Paramyxovirus; protein structure function; receptor binding; site directed mutagenesis; virus infection mechanism; virus protein

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.

以前的工作表明，中和纽卡斯尔疫病毒（NDV） 通过一组对其HN糖蛋白具有特异性的单克隆抗体（MAbs） 需要将MAb添加到具有不同功能的四个位点， 抑制性能 长期目标是更好地了解 这一现象的原因及其与人权机制的关系 中和多形包膜病毒。 具体而言，该建议旨在构建“中和 NDV HN糖蛋白的“图谱”，涉及分子的某些结构域 特定的中和机制，并可能针对特定位点 中和的效率。 这将通过决心来实现 非中和抗原变体HN的氨基酸序列 用针对糖蛋白上几个表位的单克隆抗体联合选择 通过研究这些单克隆抗体中和病毒的机制， 传染性 这将使不同的机制相互关联成为可能 和用特定HN序列中和的效率。 其他目的包括表征的持久部分的 非中和病毒及其与宿主细胞的相互作用。 可能的 副粘病毒典型的多型性在建立中的作用 将对持久性组分的含量进行调查。 此外， 将病毒-MAb与宿主细胞的复合物与病毒-MAb与宿主细胞的复合物进行对比。 未经处理的病毒。 这些方法中的每一种都将解决这一现象的不同方面 这反过来又会增加我们对 中和这组病毒。

项目成果

Amino acid substitutions in a conserved region in the stalk of the Newcastle disease virus HN glycoprotein spike impair its neuraminidase activity in the globular domain.

• DOI: 10.1099/0022-1317-80-3-749
• 发表时间: 1999-03
• 期刊: The Journal of general virology
• 作者: Zhiyu Wang;R. M. Iorio

Cooperative neuraminidase activity in a paramyxovirus.

副粘病毒中的协同神经氨酸酶活性。

• DOI: 10.1006/viro.1995.1564
• 发表时间: 1995
• 期刊: Virology.
• 作者: Mahon,PJ;Deng,R;Mirza,AM;Iorio,RM
• 通讯作者: Iorio,RM

Structure and function of a membrane anchor-less form of the hemagglutinin-neuraminidase glycoprotein of Newcastle disease virus.

新城疫病毒血凝素-神经氨酸酶糖蛋白的无膜锚定形式的结构和功能。

• 发表时间: 1993
• 期刊: The Journal of biological chemistry
• 作者: Mirza,AM;Sheehan,JP;Hardy,LW;Glickman,RL;Iorio,RM
• 通讯作者: Iorio,RM

Identification of amino acid residues important to the neuraminidase activity of the HN glycoprotein of Newcastle disease virus.

• DOI: 10.1016/0042-6822(89)90235-3
• 发表时间: 1989-11
• 期刊: Virology
• 影响因子: 3.7
• 作者: R. M. Iorio;R. Syddall;R. Glickman;Anne M. Kiel;John P. Sheehan;M. A. Bratt