Human Prion Protein with Valine 129 Prevents Expression of Variant CJD Phenotype
- 3 December 2004
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 306 (5702), 1793-1796
- https://doi.org/10.1126/science.1103932
Abstract
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.Keywords
This publication has 20 references indexed in Scilit:
- Balancing Selection at the Prion Protein Gene Consistent with Prehistoric Kurulike EpidemicsScience, 2003
- BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion proteinThe EMBO Journal, 2002
- Increased Susceptibility to Kuru of Carriers of thePRNP129 Methionine/Methionine GenotypeThe Journal of Infectious Diseases, 2001
- Strain-specific prion-protein conformation determined by metal ionsNature, 1999
- The same prion strain causes vCJD and BSENature, 1997
- Molecular analysis of prion strain variation and the aetiology of 'new variant' CJDNature, 1996
- A new variant of Creutzfeldt-Jakob disease in the UKThe Lancet, 1996
- Unaltered susceptibility to BSE in transgenic mice expressing human prion proteinNature, 1995
- Homozygous prion protein genotype predisposes to sporadic Creutzfeldt–Jakob diseaseNature, 1991
- Genetic predisposition to iatrogenic Creutzfeldt-Jakob diseaseThe Lancet, 1991