Crossing the species barrier by PrP(Sc) replication in vitro generates unique infectious prions.
Cell
; 134(5): 757-68, 2008 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-18775309
ABSTRACT
Prions are unconventional infectious agents composed exclusively of misfolded prion protein (PrP(Sc)), which transmits the disease by propagating its abnormal conformation to the cellular prion protein (PrP(C)). A key characteristic of prions is their species barrier, by which prions from one species can only infect a limited number of other species. Here, we report the generation of infectious prions by interspecies transmission of PrP(Sc) misfolding by in vitro PMCA amplification. Hamster PrP(C) misfolded by mixing with mouse PrP(Sc) generated unique prions that were infectious to wild-type hamsters, and similar results were obtained in the opposite direction. Successive rounds of PMCA amplification result in adaptation of the in vitro-produced prions, in a process reminiscent of strain stabilization observed upon serial passage in vivo. Our results indicate that PMCA is a valuable tool for the investigation of cross-species transmission and suggest that species barrier and strain generation are determined by the propagation of PrP misfolding.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Príons
/
Doenças Priônicas
/
Proteínas PrPSc
Limite:
Animals
Idioma:
En
Revista:
Cell
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos