PARAMYXOVIRUS MEMBRANE FUSION

副粘病毒膜融合

• 批准号: 6169636
• 负责人: Trudy G. Morrison
• 金额: $ 29.79万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6169636
• 关键词: Newcastle disease virus; conformation; exo alpha sialidase; glycoproteins; host organism interaction; immunoprecipitation; intermolecular interaction; membrane fusion; microorganism hemagglutinin; mutant; protein sequence; protein structure function; transfection; virus cytopathogenic effect; virus infection mechanism; virus protein

The long-term goal of this project is to determine how viral glycoproteins direct membrane fusion. Membrane fusion is a fundamental step in the life cycle of enveloped viruses and is responsible for the penetration of the host cell. Some types of viruses, notably paramyxoviruses such as Newcastle disease virus (NDV), can fuse at neutral pH with the plasma membrane of the host cell. These viruses also have the property of inducing syncytia formation, an important cytopathic effect as well as an alternate means of virus spread through a tissue. NDV membrane fusion requires the presence, in the same membrane, of the two viral glycoproteins, the HN protein and the F protein. Current evidence suggests the hypothesis that the HN protein serves to activate the activity of the F protein which is directly responsible for the fusion event. Furthermore, current evidence suggests a sequence of events leading to the formation of syncytia, and experiments to test the predictions of this model form the basis of this proposal. The project will make use of an extensive collection of mutants in both the HN and F protein genes. Specific Aims: 1. To define how the fusion protein directs the fusion between the attack and the target membranes. 2. To test the hypothesis that the HN protein functions to activate the fusion protein and to define the mechanisms involved in activation.

该项目的长期目标是确定病毒糖蛋白如何 直接膜融合。膜融合是生命的基本步骤 有包膜病毒的循环并负责渗透 宿主细胞。某些类型的病毒，特别是副粘病毒，例如 新城疫病毒 (NDV)，可在中性 pH 值下与血浆融合 宿主细胞的膜。这些病毒还具有以下特性： 诱导合胞体形成，这是一种重要的细胞病变效应，也是一种 病毒通过组织传播的替代方式。 NDV 膜融合需要在同一膜中存在 两种病毒糖蛋白，HN 蛋白和 F 蛋白。当前的 有证据表明 HN 蛋白有助于激活 直接负责融合的F蛋白的活性 事件。此外，目前的证据表明一系列事件导致 合胞体的形成，以及测试预测的实验 该模型构成了本提案的基础。该项目将利用 HN 和 F 蛋白基因的大量突变体。 具体目标： 1. 定义融合蛋白如何指导攻击之间的融合 和目标膜。 2. 检验 HN 蛋白具有激活 融合蛋白并定义参与激活的机制。