Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD

  title={Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD},
  author={John Collinge and Katie C. L. Sidle and Julie Meads and James W. Ironside and Andrew F. Hill},
Strains of transmissible spongiform encephalopathies are distinguished by differing physico-chemical properties of PrPSc, the disease-related isoform of prion protein, which can be maintained on transmission to transgenic mice. 'New variant' Creutzfeldt–Jakob disease (CJD) has strain characteristics distinct from other types of CJD and which resemble those of BSE transmitted to mice, domestic cat and macaque, consistent with BSE being the source of this new disease. Strain characteristics… 
The same prion strain causes vCJD and BSE
It is found that the biological and molecular transmission characteristics of vCJD are consistent with it being the human counterpart of BSE.
Human Prion Protein with Valine 129 Prevents Expression of Variant CJD Phenotype
Polymorphic residue 129 of human PrP dictated propagation of distinct prion strains after BSE prion infection, which may result in sporadic CJD-like or novel phenotypes in addition to vCJD, depending on the genotype of the prion source and the recipient.
Molecular analysis of ovine prion protein identifies similarities between BSE and an experimental isolate of natural scrapie, CH1641.
Biochemical evidence of strain variation in contemporary and archival brain tissue from cases of experimental BSE or experimental and natural scrapie in sheep is reported and at least one isolate of natural scrapies is found with a very similar, but not identical, PrPsc profile to BSE but which differs from BSE in its transmission characteristics to mice.
Distinct molecular phenotypes in bovine prion diseases
The existence of an atypical molecular phenotype among cattle diagnosed with BSE in France suggests either some phenotypic modifications of PrPres following infection by the BSE agent or the existence of alternative origins of such diseases in cattle.
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  • C. Weissmann
  • Biology
    The Journal of toxicological sciences
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Prnp knockout mice disrupted PrPC-related genes have played an essential role to elucidate the relationship between PrPC, a normal host gene product, and PrPSc, a protease-resistant, infectious PrP;
Transmission of the BSE Agent to Mice in the Absence of Detectable Abnormal Prion Protein
Although all of the mice injected with homogenate from BSE-infected cattle brain exhibited neurological symptoms and neuronal death, more than 55 percent had no detectable PrPres, suggesting that a further unidentified agent may actually transmit BSE.
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  • Medicine
    Canada communicable disease report = Releve des maladies transmissibles au Canada
  • 1999
New epidemic prion diseases (bovine spongiform encephalopathy and new variant Creutzfeldt–Jakob disease) have recently emerged under the active surveillance of the modern world and the risk of contracting prions from blood products or other biologicals is now a focus of worldwide concern.
Update on human prion disease.
Comparative Neuropathology of Kuru with the New Variant of Creutzfeldt‐Jakob Disease: Evidence for Strain of Agent Predominating Over Genotype of Host
The clinico‐pathologic phenotypes and the genotypes of the new variant of Creutzfeldt‐Jakob disease (vCJD) and kuru are sufficiently different to suggest that the strain of agent may play a greater role than any presumptive common route of peripherally acquired infection.
Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent
It is shown that the strain of agent from cattle affected by bovine spongiform encephalopathy (BSE) produces a characteristic pattern of disease in mice that is retained after experimental passage through a variety of intermediate species, providing strong evidence that the same agent strain is involved in both BSE and vCJD.


Non-genetic propagation of strain-specific properties of scrapie prion protein
Self-propagation of PrPSc polymers with distinct three-dimensional structures could be the molecular basis of scrapie strains, providing evidence that the protein-only model of infectious agents causing scrapie and other transmissible spon-giform encephalopathies is feasible.
Molecular genetics of prion diseases in France
The prion protein gene (PRNP) coding sequence analysis in 57 French subjects with Creutzfeldt-Jakob disease found a mutation of the PRNP coding sequence in nine subjects and found that the 129Val/Val genotype, which mainly governs susceptibility to iatrogenic CJD, does not seem to predispose to sporadic CJD.
Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy
It is proposed that PrPTME conformation could play a role in targeting TME strains to different neuron populations in which strain-specific formation occurs and is consistent with the idea thatPrPTME protein structure determines the molecular basis of strain variation.
Biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent
It is concluded that PrPTME from the HY and DY strains undergo different posttranslational modifications that could explain differences in the biochemical properties of PrPTme from the two sources.
Molecular basis of phenotypic variability in sporadc creudeldt‐jakob disease
The data indicate that the sporadic form of Creutzfeldt‐Jakob disease comprises a limited number of variants, and the methionine/valine polymorphism at codon 129 of the prion protein gene and two types of protease‐resistant prion proteins are the major determinants of these variants.
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It is shown that transgenic mice expressing human PrP in addition to mouse PrP can generatehuman PrPSc and 'human' prions, and provide a model to study experimentally the species barrier limiting BSE transmission to humans.
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Bovine spongiform encephalopathy retains a place of particular interest in the scrapie‐like or prion disease group, presenting uniquely an example of such diseases occurring as a nationwide food‐borne epidemic in Great Britain.
Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein
It is now feasible to determine whether mice devoid of PrPc can propagate prions and are susceptible to scrapie pathogenesis.
Molecular biology of prion diseases
Understanding prion diseases may advance investigations of other neurodegenerative disorders and of the processes by which neurons differentiate, function for decades, and then grow senescent.
Homozygous prion protein genotype predisposes to sporadic Creutzfeldt–Jakob disease
It is argued that homozygosity predisposes towards sporadic CJD and that this directly supports the hypothesis that interaction between prion protein molecules underlies the disease process.