Identifizierung und Charakterisierung viraler und zellulärer Faktoren, die vor einer Bornavirus-induzierten neuronalen Degeneration im Hippocampus schützen
Zusammenfassung der Projektergebnisse
Selective progressive cell death of dentate granule cells (DGC) is a common neuropathological sign in the hippocampus of Lewis and several other rat strains after neonate BDV infection. We could recapitulate this process ex vivo in hippocampal slice cultures. Few hints point to apoptotic processes as underlying mechanisms for BDV- mediated loss of granule cells. In the course of this project we provide experimental data that the BDV-mediated cell death of dentate granule cells in hippocampal slice cultures is possible caused by disturbances in autophagy dynamics rather than by the induction of apoptosis. Furthermore, using recombinant BDV encoding either Cre recombinase or GFP we provide further evidence that BFDV with impaired viral growth fail to induce DGC neuronal loss. Interestingly, we obtained very preliminary indirect evidence that BDV might be sensed by adenosine-deaminase acting on RNA such as ADAR1. Finally, we show that the eukaryotic genome has gained a riboviral polymerase gene from an ancient virus that has the potential to encode a functional RdRp.
