No Adaptation of the Prion Strain in a Heterozygous Case of Variant Creutzfeldt-Jakob Disease.

We investigated a clinical case of variant Creutzfeldt-Jakob Disease in a person heterozygous for methionine/valine at codon 129 of the prion protein gene and identified the same strain properties in variant Creutzfeldt-Jakob disease in methionine homozygous persons and in bovine spongiform encephalopathy. These results indicate no adaptation of the agent in a different genetic background.

Variant Creutzfeldt-Jakob disease strain is identical in individuals of two PRNP codon 129 genotypes.

In 2004, a subclinical case of variant Creutzfeldt-Jakob disease in a PRNP 129 methionine/valine heterozygous individual infected via blood transfusion was reported, and we established that the spleen from this individual was infectious. Since host genetics is an important factor in strain modification, the identification of variant Creutzfeldt-Jakob disease infection in a PRNP 129 methionine/valine heterozygous individual has raised the possibility that the properties of the variant Creutzfeldt-Jakob disease agent could change after transmission to this different genetic background and concerns that this could lead to a more virulent strain of variant Creutzfeldt-Jakob disease. The variant Creutzfeldt-Jakob disease strain has to date been characterized only in methionine homozygous individuals, therefore to establish whether the strain characteristics of variant Creutzfeldt-Jakob disease had been modified by the host genotype, spleen material with prion protein deposition from a PRNP 129 methionine/valine individual was inoculated into a panel of wild-type mice.

Similarities of Variant Creutzfeldt-Jakob Disease Strain in Mother and Son in Spain to UK Reference Case.

We investigated transmission characteristics of variant Creutzfeldt-Jakob disease in a mother and son from Spain. Despite differences in patient age and disease manifestations, we found the same strain properties in these patients as in UK vCJD cases. A single strain of agent appears to be responsible for all vCJD cases to date.

Increased susceptibility of transgenic mice expressing human PrP to experimental sheep bovine spongiform encephalopathy is not due to increased agent titre in sheep brain tissue.

Bovine spongiform encephalopathy (BSE) in cattle and variant Creutzfeldt-Jakob disease in humans have previously been shown to be caused by the same strain of transmissible spongiform encephalopathy agent. It is hypothesized that the agent spread to humans following consumption of food products prepared from infected cattle. Despite evidence supporting zoonotic transmission, mouse models expressing human prion protein (HuTg) have consistently shown poor transmission rates when inoculated with cattle BSE.

Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein.

The association between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health and raises the possibility that other ruminant TSEs may be transmissible to humans. In recent years, several novel TSEs in sheep, cattle and deer have been described and the risk posed to humans by these agents is currently unknown. In this study, we inoculated two forms of atypical BSE (BASE and H-type BSE), a chronic wasting disease (CWD) isolate and seven isolates of atypical scrapie into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP).

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy infection following passage in sheep.

The risk of the transmission of ruminant transmissible spongiform encephalopathy (TSE) to humans was thought to be low due to the lack of association between sheep scrapie and the incidence of human TSE. However, a single TSE agent strain has been shown to cause both bovine spongiform encephalopathy (BSE) and human vCJD, indicating that some ruminant TSEs are transmissible to humans. While the transmission of cattle BSE to humans in transgenic mouse models has been inefficient, indicating the presence of a significant transmission barrier between cattle and humans, BSE has been transmitted to a number of other species.

Host PrP glycosylation: a major factor determining the outcome of prion infection.

The expression of the prion protein (PrP) is essential for transmissible spongiform encephalopathy (TSE) or prion diseases to occur, but the underlying mechanism of infection remains unresolved. To address the hypothesis that glycosylation of host PrP is a major factor influencing TSE infection, we have inoculated gene-targeted transgenic mice that have restricted N-linked glycosylation of PrP with three TSE strains. We have uniquely demonstrated that mice expressing only unglycosylated PrP can sustain a TSE infection, despite altered cellular location of the host PrP.

Electro-elution, a novel method to remove transmissible spongiform encephalopathy-associated PrPSc from stainless steel surgical instruments.

Iatrogenic transmission of transmissible spongiform encephalopathies (TSEs) has been demonstrated via surgical instruments and there is concern over the efficacy of conventional decontamination techniques used to reprocess reusable instruments. This paper describes the development of a novel cleaning method, 'electro-elution', to remove TSE disease-specific abnormal protein PrP(Sc) from the surface of stainless steel surgical instruments. The electro-elution process subjects the stainless steel instrument to an electrical current in the presence of an electrolytic buffer to remove protein deposits.

Predicting susceptibility and incubation time of human-to-human transmission of vCJD.

Background: Identification of possible transmission of variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion has caused concern over spread of the disease within the human population. We aimed to model iatrogenic spread to enable a comparison of transmission efficiencies of vCJD and bovine spongiform encephalopathy (BSE) and an assessment of the effect of the codon-129 polymorphism on human susceptibility.

Methods: Mice were produced to express human or bovine prion protein (PrP) by direct replacement of the mouse PrP gene.