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Lassa virus assembly and release mediated by interplay of viral proteins and cellular factors
Antragsteller
Professor Dr. Wolfgang Garten
Fachliche Zuordnung
Virologie
Förderung
Förderung von 2005 bis 2012
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 13204846
The purpose of the project is the understanding of the final Lassa virus replication steps, assembly and packaging of viral components, and budding and release of virus particles from host cells. Lassa virus, a member of Arenaviridae consists of two helical ribonucleocapsids surrounded by a cell-derived, lipid-containing envelope, which is lined with a matrix protein and spiked with only one glycoprotein. We recently identified Lassa virus Z protein as a viral matrix protein. It contains two tetrapeptide motifs known as late domains , which are involved in recruitment of cellular factors which normally function in vesicular transport. Solely expressed recombinant Z forms virus-like particles (VLPs). Thus, Z is a major player of virus budding. Our goals are: (i) identification and characterization of cellular proteins interacting with Lassa viral proteins at different maturation stages, (ii) interaction of Z and other viral proteins with detergent-insoluble glycosphingolipid-enriched membrane domains (DIGs), (iii) oligomerization and crystal structure of Z, together with cellular factors. Insight in virus maturation on structural basis will allow designing inhibitors which are able to block viral infection and thus may have therapeutic potential.
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