In this review I covered recent data on the vCJD and BSE epidemic, the mode of BSE spreading to humans and, finally, the data on the PRNP analogue--the doppel gene (PRND).
Molecular analysis of PrP(Sc) (the scrapie isoform of PrP) from cerebellar tissue demonstrated a novel PrP(Sc) type similar to that seen in vCJD (PrP(Sc) type 4).
For example, cross-sequence transmission of bovine spongiform encephalopathy (BSE) prions to human generated variant Creutzfeldt-Jakob disease (vCJD) prions which retained the transmissibility to mice expressing bovine PrP.
The single monkey infected with BASE had a shorter survival, and a different clinical evolution, histopathology, and prion protein (PrPres) pattern than was observed for either classical BSE or vCJD-inoculated animals.
Western blot analysis of PrP(Sc) in the brain in vCJD tissue shows a uniform isotype, with a glycoform ratio characterized by predominance of the diglycosylated band, distinct from sporadic CJD.
These data argue that human PRNP 129 heterozygotes will be more susceptible to infection with vCJD prions than to cattle BSE prions and may present with a neuropathological phenotype distinct from vCJD.
We show that one such technique, protein misfolding cyclic amplification (PMCA), can amplify vCJDPrP(Sc) from human brain tissue, and that the degree of amplification is dependent upon the substrate PRNP codon 129 polymorphism.
Correlation of polydispersed prion protein and characteristic pathology in the thalamus in variant Creutzfeldt-Jakob disease: implication of small oligomeric species.
The presence of abnormal, disease-related prion protein (PrP<sup>D</sup>) has recently been demonstrated by protein misfolding cyclic amplification (PMCA) in urine of patients affected with variant Creutzfeldt-Jakob disease (vCJD), a prion disease typically acquired from consumption of prion contaminated bovine meat.
The patient was a heterozygote at codon 129 of PRNP, suggesting that susceptibility to vCJD infection is not confined to the methionine homozygous PRNP genotype.
In contrast, variant Creutzfeldt-Jakob disease (vCJD), which results from oral exposure to the agent of bovine spongiform encephalopathy, is a highly stereotyped disease, that, until now, has only occurred in patients who are methionine homozygous at codon 129 of the PrP gene.
Besides the molecular typing of protease-resistant PrP in the brain, transmission studies using knock-in mice carrying bovine PrP may aid the differential diagnosis of secondary vCJD infection, especially in individuals with the 129V/V genotype.
Abnormal prion protein (PrP<sup>TSE</sup>) extracted from the brains of vCJD-infected TgBo110 mice displayed different glycosylation profiles and had greater resistance to denaturation by guanidine hydrochloride than PrP<sup>TSE</sup> from infected wild-type mice or from either inoculum.
Archival kuru and recent variant Creutzfeldt-Jakob disease (vCJD) cases reveal distinct lesional differences, particularly with respect to prion protein, suggesting that the strain of agent is important in determining the phenotype.
Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain.
This minority type 1 PrP(Sc) was found in all 21 cases of variant Creutzfeldt-Jakob disease tested, irrespective of brain region examined, and was also present in the variant Creutzfeldt-Jakob disease tonsil.
Genotype frequencies at codon 129 of the prion protein gene in Brazil: Implications in susceptibility to variant Creutzfeldt-Jakob disease compared to European and Asian populations.
Further studies are required to develop more sensitive means of detection of disease-associated prion protein in blood; such techniques could also be employed for screening purposes, both individually and to help ascertain more precisely the likely numbers of future cases of vCJD.