NR ARCT
AU Eiden,M.; Groschup,M.H.
TI A synergistic effect of BSE and Me7 scrapie prions enhances the cell-free conversion of cellular prion protein
QU TSE-Forum, 4. Kongress - Nationale TSE-Forschungsplattform, Düsseldorf 28.10.-29.10.2004, Vortrag V-10
PT Konferenz-Vortrag
AB
Prion diseases or transmissible spongiform encephalopathies (TSEs) are characterized by a structural re-arrangement of the cellular PrPc into an abnormal form which is designated PrPsc or PrPres. This process is also called conversion and leads to modified biochemical properties of abnormal prion protein: Partial resistance to proteinase K, aggregation and subsequent fibril forming.
In a cell-free assay the conversion reaction can be imitated by coincubating highly purified PrPc molecules together with PrPsc seeds in an appropriate conversion buffer. Under these conditions we can show, that PrPsc itself can induce the conversion of PrPc into a partial proteinase K resistant form PrPres. Newly converted PrPres can be detected by an antibody that discriminates between PrPres and PrPsc. In our assay we use procaryoticly expressed PrPc as substrate and mouse passaged scrapie and BSE strains/isolates as seeds. Intrigueingly, even differences in the molecular masses of PrPres (after PK treatment) of BSE and the scrapie strains are transmitted to the newly formed PrPres fragments which illustrates the efficacy of PrPsc to transduce its specific conformation even in a cell-free environment.
Double incubation of a mouse passaged scrapie and BSE strain/isolates resulted in two PrPres fragments which were distinct in their molecular masses. Moreover, the yield of newly converted PrPres in such double incubations, was higher in comparison to singleton incubation reactions indicating a synergistic interaction between the two TSE strains.
AD Martin Eiden and Martin H. Groschup, Institute for Novel and Emerging Infectious Diseases at the Friedrich-Loeffler-Institut, Isle of Riems
SP englisch
PO Deutschland
OR Tagungsband