NR AUQQ
AU Giese,A.; Weber,P.; Piening,N.; Mitteregger,G.; Thomzig,A.; Beekes,M.; Kretzschmar,H.A.
TI Cell-free formation of misfolded prion protein with genuine prion infectivity
QU TSE-Forum, 6. Kongress - Nationale TSE-Forschungsplattform, Greifswald 26.6.-28.6.2006, Vortrag V-09
PT Konferenz-Vortrag
AB The structural conversion of PrPc to protease-resistant PrP (PrPres) has been modelled in vitro by protein misfolding cyclic amplification (PMCA). However, the phenomenon that PrPres generated in the test tube is less infectious than prion particles generated in vivo has cast doubt on the "protein-only" hypothesis of prion propagation and has supported theories invoking additional species of infectious PrP or further agent-associated factors. Using serial transmission PMCA (sPMCA) we have been able to show that PrPres amplification in vitro follows an autocatalytic mechanism, which is in accordance with the "protein-only" hypothesis of prion propagation. We now show that amplification of misfolded prion protein by sPMCA generates new infectious units. Importantly, the PrPres generated in vitro is as infectious as authentic brain-derived PrPsc provided that confounding effects related to differences in the size distribution of PrP aggregates and consecutive differences in regard to biological clearance are abrogated by prion delivery on suitable nitrocellulose (NC) carrier particles. This finding rebuts one of the main arguments against the "protein-only" hypothesis.
AD Armin Giese, Petra Weber, Niklas Piening, Gerda Mitteregger, Hans A. Kretzschmar, Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 23, 81377 München, Germany; Achim Thomzig, Michael Beekes, P24 - Transmissible Spongiforme Enzephalopathien, Robert-Koch-Institut, Nordufer 20, 13353 Berlin, Germany
SP englisch
PO Deutschland
OR Tagungsband