Detailseite
Projekt
Membrane budding by rabies virus matrix- and phosphoprotein
Antragsteller
Professor Dr. Karl-Klaus Conzelmann; Professor Dr. Stefan Finke
Fachliche Zuordnung
Virologie
Förderung
Förderung von 2005 bis 2015
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 13166192
Assembly and budding of Rabies virus (RV) and related Rhabdoviruses takes place at the plasma membrane. The major driving force of envelopment and membrane budding is the viral matrix protein M which binds membranes, virus cores and glycoproteins, and which is active in membrane bending and pinching off membrane vesicles. The active process of ¿exocytosis¿ involves cellular membrane-associated factors binding to ¿late domains¿ iden-tified in M or M-like proteins of various enveloped viruses. Of the 2 classical late domain motifs identified in RV M, however, none is essential, and RV M budding is independent of the factor VPS4 downstream of ESCRT, in contrast to viruses budding from internal membranes, such as Ebola virus or HIV. This suggests the presence of so far unidentified late domains in RV M, or the use of alternative, so far unknown mechanisms for viral or vesicle exocytosis at the plasma membrane. In the proposed project, we will dissect the multiple functions of RV M by screening a comprehensive bank of M Ala-scan mutants for complementation of defined steps of the life cycle of defective RVs designed by reverse genetics. In a hierarchical system mutants will be identified that are competent in regulating viral RNA synthesis, binding and con-densation of viral cores and glycoproteins, but have discrete defects in (i) membrane bind-ing (ii) ¿sorting, (iii) -bending and (iv) vesicle pinching-off. In comparison with wtM, the mutants will shed light on the identity of M domains and cellular interacting factors and the molecular mechanisms of viral exocytosis at the plasma membrane.
DFG-Verfahren
Schwerpunktprogramme
