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Molecular characterization of the Nyamaninivirus (NYMV): Identification and analysis of viral protein functions in the NYMV replication cycle
Antragsteller
Professor Dr. Peter Stäheli, seit 11/2010
Fachliche Zuordnung
Virologie
Förderung
Förderung von 2010 bis 2013
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 179119887
The Nyamaninivirus (NYMV) was recently recognized as member of the order Mononegavirales and belongs to a novel taxon, the Nyaviridae. The NYMV genome encodes for at least six proteins, which share only weak (N and L) or no detectable homology with other viral or cellular proteins. The lack of homology prevented the clear assignment of protein function to the remaining four proteins and raises questions about the structural basis of these functions. To analyze the biology of the Nyaviridae we assembled a cDNA encoding the NYMV full-length antigenome and expression vectors for the various NYMV proteins. We found that proteins encoded by transcription units 1(N), 3 and 6 (L) are essential and sufficient for NYMV recovery from cDNA indicating an atypical gene arrangement, in which the potential phosphoprotein adopts the third position within the transcription gradient. We further found that NYMV replication activates IFN-β but not IFN-α transcription and is insensitive to exogenously added IFN-α, indicating that NYMV interferes with signaling and activity of the innate immune system. The proposed projects aim at defining protein function in the viral replication cycle and in the prevention of inhibitory host cell responses. We will analyze the consequences of the atypical gene arrangement for viral replication efficacy, particle formation and pathogenesis. The results of our preliminary studies support the conclusion that NYMV belongs to a novel virus family within the order Mononegavirales, and we are the first laboratory with the tools to study its biology.
DFG-Verfahren
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Ehemaliger Antragsteller
Privatdozent Dr. Urs Schneider, bis 11/2010