Rolle der Transmembran-Segmente von Masern-Glykoproteinen im Aufbau der viralen Hülle und der Gebrauch fremder Glykoproteine auf Masernviren für eine divalente Impfung

麻疹糖蛋白跨膜片段在病毒包膜组装中的作用以及在麻疹病毒上使用外源糖蛋白进行二价疫苗接种

• 批准号: 5442832
• 负责人: Privatdozent Dr. Michael D. Mühlebach
• 金额: --
• 依托单位: Abteilung Veterinärmedizin
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2005-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5442832?language=en
• 关键词: Rolle; der; Transmembran; Segmente; von

Understanding the interactions supporting envelope assembly is of central importance for the development of multivalent measles virus (MV)-based vaccines and for vector targeting. Depending on the circumstances, the incorporation of foreign proteins in the MV envelope may or not be envisaged. Presentation of a foreign glycoprotein regularly arranged in a viral particle may induce a more robust immune response than secretion of the same protein or its expression on the cell membrane. We have previously shown that the membrane-distal amino acids in the MV fusion (F) and hemagglutinin (H) protein cytoplasmic tail modulate the efficiency of these proteins in viral particles (Cathomen et al., J. Virol. 1998). We also have indications that the transmembrane (TM) segment of these glycoproteins may contribute to efficient particle incorporation (M.Rager et al., unpublished). In this work we aim at identifying the residues in the F and H proteins important for envelope incorporation, and to vrify whether the identified amino acids have an effect on the incorporation of selected foreign glycoproteins into MV particles. Ideally, these experiments will result in the production of a set of TM and cytoplasmic tail mutants that are "portable" and can be used to confer graded efficieny of incorporation of foreign glycoproteins into MV particles. In a third set of experiments, we plan to measure the magnitude of the immune response induced by recombinant MVs expressing a reporter glycoprotein in different configurations: secreted, displayed on viral particles, or on the cell surface.

了解支持包膜组装的相互作用对于开发基于多价麻疹病毒（MV）的疫苗和载体靶向至关重要。根据情况，可以设想或不设想将外源蛋白掺入MV包膜中。在病毒颗粒中规则排列的外源糖蛋白的呈递可以诱导比相同蛋白质的分泌或其在细胞膜上的表达更强的免疫应答。我们先前已经表明，MV融合（F）和血凝素（H）蛋白质胞质尾中的膜远端氨基酸调节这些蛋白质在病毒颗粒中的效率（Cathomen等人，J. Virol. 1998年）。我们也有迹象表明，这些糖蛋白的跨膜（TM）区段可能有助于有效的颗粒掺入（M.Rager等人，未出版）。在这项工作中，我们的目标是确定的F和H蛋白的残基的包膜掺入的重要性，并vrify是否已确定的氨基酸对选定的外源糖蛋白到MV颗粒的掺入的影响。理想地，这些实验将导致产生一组TM和胞质尾突变体，其是“便携的”并且可用于赋予将外源糖蛋白掺入MV颗粒中的分级效率。在第三组实验中，我们计划测量以不同构型表达报告糖蛋白的重组MV诱导的免疫应答的幅度：分泌的、在病毒颗粒上展示的或在细胞表面上展示的。