Identification and functional characterization of cellular interaction partners of the ribonucleoprotein complex of Borna Disease Virus

• Applicant: Professor Dr. Martin Schwemmle
• Subject Area: Virology
• Term: from 2005 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5449165

Borna Diesease Virus (BDV) persistently infects the central nervous system and can either cause immunopathology or neurodevelopmental damage in the absence of inflammation. We hypothesize that the BDV replication machinery depends on the interaction with cellular host factors. We further hypothesize that the interaction between viral and cellular factors can trigger neuronal damage. This project therefore focuses on the identification and functional characterization of cellular factors involved in BDV replication and pathogenesis. In a proteomic-based approach, we want to isolate native viral ribonucleoprotein complexes (RNPs), followed by identification of co-purified cellular interactions partners (CIP) using mass spectrometric analysis. Binding studies should further help to define BDV protein mutants that fail to interact with specific CIPs. If these mutants still support BDV minireplicon transcription, we will rescue the corresponding virus mutants, with the help of our newly established reverse genetic system of BDV, to study replication and pathogenesis. In case BDV protein mutants turn out to be non-functional in the minireplicon assay, we will determine whether the corresponding CIP are essential for viral replication. Initially, we will study the role of a known cellular interaction partner of the viral phosphoprotein, HMBG1, a neurite outgrowth factor. Functional characterization of CIP will not only provide important insights into viral replication strategies but also reveal mechanistic details of virus-induced disorders of the CNS.

• DFG Programme: Research Grants