Measles virus M protein trafficking: identification of pathways, functional domains, modifications and cell specificity

麻疹病毒(MV)的细胞类型特异性限制包括成熟的专业抗原提呈细胞(单核/巨噬细胞和树突状细胞(DC))缺乏传染性病毒的产生。由于M蛋白是颗粒产生的驱动力，该项目旨在研究MV野生型和疫苗株衍生的M蛋白在许可细胞(成纤维细胞)和半许可细胞(成熟DC)中的翻译后修饰、寡聚、半衰期、细胞内转运以及与特殊细胞内(多囊泡小体，DALIS)和质膜(脂筏)的关联。正如我们最近观察到的由MV M蛋白驱动的病毒样颗粒的形成，该蛋白中的L结构域以及参与M蛋白分选的细胞相互作用蛋白将被确定。随着重组病毒的产生，L结构域对成纤维细胞和成熟DC出芽的贡献将被分析。这些研究将有助于更深入地了解M蛋白在MV形态发生中的基本作用，这一过程尚未得到很好的表征，并将通过DC等特殊细胞类型的细胞内环境来潜在地改变这一过程。由于其他病毒对成熟DC中病毒复制的限制也是已知的，后一种情况可能反映了避免T细胞感染扫描DC以识别抗原的一般机制。

Cell type specific restrictions of measles virus (MV) include a lack of infectious virus production as seen in maturing professional antigen presenting cells (monocyte/macrophages and dendritic cells (DCs)). Since M proteins are known as driving forces for particle production the project aims to study posttranslational modifications, oligomerisation, half life, intracellular trafficking and association with specialised intracellular (multivesicular bodies, DALIS) and plasma membrane (lipid raft) compartments for wild-type and vaccine strain derived M proteins of MV in permissive (fibroblasts) and semipermissive cells (maturing DCs). As we recently observed formation of virus like particles driven by the MV M protein, L domains within this protein will be identified as well as cellular interacting proteins involved in M protein sorting. With the generation of recombinant viruses the contribution of the L domains for budding from fibroblasts and maturing DCs will be analysed. These studies will lead to a deeper understanding of the basic role of M protein in MV morphogenesis which is not well characterised and to potential alterations of this process by the intracellular milieu of specialised cell types such as DCs. As restrictions of viral replication in mature DCs are also known for other viruses, the latter situation probably reflects a general mechanism to avoid infection of T cells scanning DCs for antigen recognition.