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

• Antragsteller: Privatdozent Dr. Michael D. Mühlebach
• Fachliche Zuordnung: Virologie
• Förderung: Förderung von 2005 bis 2006
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5442832

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transmembrane (TM) segment of these glycoproteins may contribute to efficient particle incorporation (M.Rager et al., unpublished).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.

• DFG-Verfahren: Forschungsstipendien