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

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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.