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Published Online November 11, 2004
Science DOI: 10.1126/science.1103932

Reports

Submitted on August 11, 2004
Accepted on October 22, 2004

Human Prion Protein with Valine 129 Prevents Expression of Variant CJD Phenotype

Jonathan D. F. Wadsworth 1, Emmanuel A. Asante 1, Melanie Desbruslais 1, Jacqueline M. Linehan 1, Susan Joiner 1, Ian Gowland 1, Julie Welch 1, Lisa Stone 1, Sarah E. Lloyd 1, Andrew F. Hill 1{dagger}, Sebastian Brandner 1, John Collinge 1*

1 Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.

* To whom correspondence should be addressed.
John Collinge , E-mail: j.collinge{at}prion.ucl.ac.uk

{dagger}Present address: Department of Biochemistry and Molecular Biology and Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia.

Variant Creutzfeldt-Jakob disease (vCJD) is a unique and highly distinctive clinicopathological and molecular phenotype of human prion disease associated with infection with bovine spongiform encephalopathy (BSE)-like prions. Here, we found that generation of this phenotype in transgenic mice required expression of human prion protein (PrP) with methionine 129. Expression of human PrP with valine 129 resulted in a distinct phenotype and, remarkably, persistence of a barrier to transmission of BSE-derived prions on subpassage. Polymorphic residue 129 of human PrP dictated propagation of distinct prion strains after BSE prion infection. Thus, primary and secondary human infection with BSE-derived prions may result in sporadic CJD-like or novel phenotypes in addition to vCJD, depending on the genotype of the prion source and the recipient.


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