NR AXKH
AU Castilla,J.; Nonno,R.; Fernandez-Borges,N.; Di Bari,M.A.; Cosseddu,G.M.; de Castro,J.; Chiappini,B.; Vaccari,G.; Agrimi,U.
TI De Novo Generation of Prions in a Cell-free System
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Oral Abstracts FC7.4
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Vortrag
AB Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative disorders affecting both humans and animals. There is no available treatment or therapy for these fatal diseases. The infectious agent associated with TSEs (termed prion) appears to be composed uniquely of a protein, which is a conformationallymodified version (PrPsc) of the cellular prion protein (PrPc). The disease is propagated by the conversion of host PrPc into PrPsc induced by small quantities of PrPsc. Interestingly, prions occur in the form of different strains that show distinct biological and physicochemical properties. TSEs can have diverse origins, including genetic, sporadic (putatively spontaneous) and infectious. The occurrence of sporadic cases of prion diseases in humans and maybe in other species, i.e. atypical bovine spongiform encephalopathy (BSE) in European and USA cattle and atypical scrapie cases in sheep suggest that spontaneous prion diseases may happen infrequently but ubiquitously. However, there are no reported cases of spontaneously-occurring prion disease in experimental wild-type rodent models. We have used a novel technique, Protein Misfolding Cyclic Amplification (PMCA) to rapidly propagate prions in the test tube, using normal brain homogenate as substrate. Prions propagated in vitro are infectious in vivo and maintain their prion strain specificity. PMCA has been used to efficiently amplify a variety of prion strains from mouse, hamster, bank vole, deer, cattle, sheep and human. Therefore, to mimic spontaneous generation of infectivity in vitro becomes one of the most important challenges in the prion field. We show here, for the first time, the de novo generation of infectious prions from bank voles (Clethrionomys glareolus) starting with non-infectious brain homogenates. Several biochemically different prion strains were generated using two different wild-type vole genotypes. The de novo in vitro generated PrPsc was highly infectious after its inoculation in bank voles. We show an extensive characterization of this "spontaneous" phenomenon.
AD J. Castilla, N. Fernández-Borges, J. de Castro, Scripps Florida, Infectology, USA; R. Nonno, M.A. Di Bari, G.M. Cosseddu, B. Chiappini, G. Vaccari, U. Agrimi, Istituto Superiore di Sanitá, Food Safety and Veterinary Public Health, Italy
SP englisch
PO Schottland