Cell-free propagation of prion strains

Castilla J.; Morales R.; Saa, P; Barria, M.; Gambetti, P; Soto C.

Abstract

Prions are the infectious agents responsible for prion diseases, which appear to be composed exclusively by the misfolded prion protein (PrP Sc). Disease is transmitted by the autocatalytic propagation of PrPSc misfolding at the expense of the normal prion protein. The biggest challenge of the prion hypothesis has been to explain the molecular mechanism by which prions can exist as different strains, producing diseases with distinguishable characteristics. Here, we show that PrPSc generated in vitro by protein misfolding cyclic amplification from five different mouse prion strains maintains the strain-specific properties. Inoculation of wild-type mice with in vitro-generated PrPSc caused a disease with indistinguishable incubation times as well as neuropathological and biochemical characteristics as the parental strains. Biochemical features were also maintained upon replication of four human prion strains. These results provide additional support for the prion hypothesis and indicate that strain characteristics can be faithfully propagated in the absence of living cells, suggesting that strain variation is dependent on PrPSc properties. © 2008 European Molecular Biology Organization | All Rights Reserved.

Más información

Título según WOS: Cell-free propagation of prion strains
Título según SCOPUS: Cell-free propagation of prion strains
Título de la Revista: EMBO JOURNAL
Volumen: 27
Número: 19
Editorial: WILEY-BLACKWELL
Fecha de publicación: 2008
Página de inicio: 2557
Página final: 2566
Idioma: English
URL: http://emboj.embopress.org/cgi/doi/10.1038/emboj.2008.181
DOI:

10.1038/emboj.2008.181

Notas: ISI, SCOPUS