MECHANISMS OF MOUSE HEPATITIS VIRUS HOST RANGE EXPANSION

小鼠肝炎病毒宿主范围扩展的机制

• 批准号: 8168019
• 负责人: Willie McRoy
• 金额: $ 4.23万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168019
• 关键词: Binding; Biochemical; Cell membrane; Cells; Chimeric Proteins; Computer Retrieval of Information on Scientific Projects Database; Coronavirus; Environment; Funding; Fuzeon; Goals; Grant; Influenza; Institution; Lead; Membrane Fusion; Modeling; Murine hepatitis virus; Mutation; Peptides; Pharmaceutical Preparations; Process; Property; Proteins; Research; Research Personnel; Resources; Source; United States National Institutes of Health; Virus; mutant; pressure

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The model coronavirus Mouse Hepatitis Virus (MHV) is dependent upon its Spike protein for target cell binding. Once bound, Spike directs subsequent virus-cell membrane fusion thus leading to entry and by extension regulating host range. Spike protein displays the features of a Class I fusion protein, similar to the fusion proteins of Influenza. Prior research with MHV and other Class I viruses has demonstrated that mutations in and adjacent to conserved heptad repeat regions (regions vital to the fusion process) can lead to altered host range. The hypothesis is that the Spike protein has an inherent "slack" in the fusion mechanism that may be exposed under certain selective environments leading to altered host range. This project has two goals. The first is to examine the biochemical properties of Spike proteins from previously isolated MHV host range mutants. The second will examine what, if any, mutations result when selective pressure is applied to the heptad repeats using a fusion inhibiting peptide, similar to the drug Fuzeon. By combining these studies, a clearer picture of how MHV can cross the species barrier should be developed and possibly extended to other Class I viruses.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 模型冠状病毒小鼠肝炎病毒（MHV）依赖于其刺突蛋白用于靶细胞结合。 一旦结合，刺突引导随后的病毒-细胞膜融合，从而导致进入并通过延伸调节宿主范围。 刺突蛋白显示I类融合蛋白的特征，类似于流感的融合蛋白。 先前对MHV和其他I类病毒的研究表明，保守的七肽重复区（对融合过程至关重要的区域）中及其附近的突变可导致宿主范围改变。 假设是刺突蛋白在融合机制中具有固有的“松弛”，其可能暴露在某些选择性环境下，导致宿主范围改变。 这个项目有两个目标。 第一个是检查以前分离的MHV宿主范围突变体的刺突蛋白的生化特性。 第二个将检查当使用融合抑制肽（类似于药物Fuzeon）对七肽重复序列施加选择性压力时会产生什么样的突变（如果有的话）。 通过结合这些研究，应该开发出MHV如何跨越物种屏障的更清晰的图片，并可能扩展到其他I类病毒。