Article
- The EMBO Journal (2008) 27, 2557 - 2566
- doi:10.1038/emboj.2008.181
Published online: 18 September 2008
Subject Category:
Cell-free propagation of prion strains
Joaquín Castilla1,a, Rodrigo Morales1,2,a, Paula Saá1,3, Marcelo Barria1, Pierluigi Gambetti4 and Claudio Soto1
- Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA
- University of Chile, Santiago, Chile
- Centro de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain
- Case Western Reserve University, Cleveland, OH, USA
Correspondence to:
Claudio Soto, Department of Neurology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA. Tel.: +1 409 747 0017; Fax: +1 409 747 0020; E-mail: clsoto@utmb.edu
aThese authors contributed equally to this work
Received 24 December 2007; Accepted 13 August 2008
Abstract
Prions are the infectious agents responsible for prion diseases, which appear to be composed exclusively by the misfolded prion protein (PrPSc). 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.
Keywords:
- infectious agent,
- prions,
- protein misfolding,
- strains,
- transmissible spongiform encephalopathies
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