Crossing the species barrier by PrPSc replication in vitro generates unique infectious Prions
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2008-09-05Metadata
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Castilla, Joaquín
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Crossing the species barrier by PrPSc replication in vitro generates unique infectious Prions
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Abstract
Prions are unconventional infectious agents composed exclusively of misfolded prion protein (PrPSc), which transmits the disease by propagating its abnormal conformation to the cellular prion protein (PrPC). 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 PrPSc misfolding by in vitro PMCA amplification. Hamster PrPC misfolded by mixing with mouse PrPSc 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.
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This research was supported in part by National Institutes of Health grants
R01NS049173 and P01AI77774 to C.S. C.S. is a founder of Amprion, Inc., a company focused on the development of a diagnosis for prion diseases
through the use of the PMCA technology.
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URI: https://repositorio.uchile.cl/handle/2250/128136
DOI: 10.1016/j.cell.2008.07.030
ISSN: 0092-8674
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CELL Volume: 134 Issue: 5 Pages: 757-768 Published: SEP 5 2008
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