scholarly journals Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey

BMJ ◽  
2013 ◽  
Vol 347 (oct15 5) ◽  
pp. f5675-f5675 ◽  
Author(s):  
O. N. Gill ◽  
Y. Spencer ◽  
A. Richard-Loendt ◽  
C. Kelly ◽  
R. Dabaghian ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Large Scale ◽  
Spongiform Encephalopathy ◽  
Large Scale Survey

scholarly journals Presence of subclinical infection in gene-targeted human prion protein transgenic mice exposed to atypical bovine spongiform encephalopathy

2013 ◽  
Vol 94 (12) ◽  
pp. 2819-2827 ◽  
Author(s):  
Rona Wilson ◽  
Karen Dobie ◽  
Nora Hunter ◽  
Cristina Casalone ◽  
Thierry Baron ◽  
...  
Keyword(s):  
Human Health ◽  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Disease Transmission ◽  
Large Scale ◽  
Single Agent ◽  
Diagnostic Methods ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Human Prion Protein

The transmission of bovine spongiform encephalopathy (BSE) to humans, leading to variant Creutzfeldt–Jakob disease has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health. Until recently, TSE disease in cattle was thought to be caused by a single agent strain, BSE, also known as classical BSE, or BSE-C. However, due to the initiation of a large-scale surveillance programme throughout Europe, two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H have since been discovered. To model the risk to human health, we previously inoculated these two forms of atypical BSE (BASE and BSE-H) into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP) (HuTg) but were unable to detect any signs of TSE pathology in these mice. However, despite the absence of TSE pathology, upon subpassage of some BASE-challenged HuTg mice, a TSE was observed in recipient gene-targeted bovine PrP Tg (Bov6) mice but not in HuTg mice. Disease transmission from apparently healthy individuals indicates the presence of subclinical BASE infection in mice expressing human PrP that cannot be identified by current diagnostic methods. However, due to the lack of transmission to HuTg mice on subpassage, the efficiency of mouse-to-mouse transmission of BASE appears to be low when mice express human rather than bovine PrP.

scholarly journals Discriminating Scrapie and Bovine Spongiform Encephalopathy Isolates by Infrared Spectroscopy of Pathological Prion Protein

2004 ◽  
Vol 279 (32) ◽  
pp. 33847-33854 ◽  
Author(s):  
Achim Thomzig ◽  
Sashko Spassov ◽  
Manuela Friedrich ◽  
Dieter Naumann ◽  
Michael Beekes
Keyword(s):  
Infrared Spectroscopy ◽  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Spongiform Encephalopathy

scholarly journals First Report of the Potential Bovine Spongiform Encephalopathy (BSE)-Related Somatic Mutation E211K of the Prion Protein Gene (PRNP) in Cattle

2020 ◽  
Vol 21 (12) ◽  
pp. 4246 ◽  
Author(s):  
Sae-Young Won ◽  
Yong-Chan Kim ◽  
Byung-Hoon Jeong
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Somatic Mutation ◽  
Prion Disease ◽  
In Silico ◽  
Somatic Mutations ◽  
Protein Gene ◽  
Prnp Gene ◽  
Spongiform Encephalopathy ◽  
Prion Protein Gene

Bovine spongiform encephalopathy (BSE) is a prion disease characterized by spongiform degeneration and astrocytosis in the brain. Unlike classical BSE, which is caused by prion-disease-contaminated meat and bone meal, the cause of atypical BSE has not been determined. Since previous studies have reported that the somatic mutation in the human prion protein gene (PRNP) has been linked to human prion disease, the somatic mutation of the PRNP gene was presumed to be one cause of prion disease. However, to the best of our knowledge, the somatic mutation of this gene in cattle has not been investigated to date. We investigated somatic mutations in a total of 58 samples, including peripheral blood; brain tissue including the medulla oblongata, cerebellum, cortex, and thalamus; and skin tissue in 20 individuals from each breed using pyrosequencing. In addition, we estimated the deleterious effect of the K211 somatic mutation on bovine prion protein by in silico evaluation tools, including PolyPhen-2 and PANTHER. We found a high rate of K211 somatic mutations of the bovine PRNP gene in the medulla oblongata of three Holsteins (10% ± 4.4%, 28% ± 2%, and 19.55% ± 3.1%). In addition, in silico programs showed that the K211 somatic mutation was damaging. To the best of our knowledge, this study is the first to investigate K211 somatic mutations of the bovine PRNP gene that are associated with potential BSE progression.

scholarly journals Synergistic and strain-specific effects of bovine spongiform encephalopathy and scrapie prions in the cell-free conversion of recombinant prion protein

2006 ◽  
Vol 87 (12) ◽  
pp. 3753-3761 ◽  
Author(s):  
Martin Eiden ◽  
Gottfried J. Palm ◽  
Winfried Hinrichs ◽  
Ulrich Matthey ◽  
Ralph Zahn ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
De Novo ◽  
Proteinase K ◽  
Spongiform Encephalopathy ◽  
Cooperative Action ◽  
Specific Effects ◽  
Scrapie Strains ◽  
Recombinant Prion Protein

This study describes the conversion of murine PrPC by PrPSc from three different mouse scrapie strains (ME7, 87V and 22A) and from a mouse-passaged bovine spongiform encephalopathy (BSE) strain (BSE/Bl6). This was demonstrated by a modified, non-radioactive, cell-free conversion assay using bacterial prion protein, which was converted into a proteinase K (PK)-resistant fragment designated PrPres. Using this assay, newly formed PrPres could be detected by an antibody that discriminated de novo PrPres and the original PrPSc seed. The results suggested that PrPres formation occurs in three phases: the first 48 h when PrPres formation is delayed, followed by a period of substantially accelerated PrPres formation and a plateau phase when a maximum concentration of PrPres is reached after 72 h. The conversion of prokaryotically expressed PrPC by ME7 and BSE prions led to unglycosylated, PK-digested, abnormal PrPres fragments, which differed in molecular mass by 1 kDa. Therefore, prion strain phenotypes were retained in the cell-free conversion, even when recombinant PrPC was used as the substrate. Moreover, co-incubation of ME7 and BSE prions resulted in equal amounts of both ME7- and BSE-derived PrPres fragments (as distinguished by their different molecular sizes) and also in a significantly increased total amount of de novo-generated PrPres. This was found to be more than twice the amount of either strain when incubated separately. This result indicates a synergistic effect of both strains during cell-free conversion. It is not yet known whether such a cooperative action between BSE and scrapie prions also occurs in vivo.

scholarly journals Prion Type-Dependent Deposition ofPRNPAllelic Products in Heterozygous Sheep

2015 ◽  
Vol 90 (2) ◽  
pp. 805-812 ◽  
Author(s):  
J. P. M. Langeveld ◽  
J. G. Jacobs ◽  
N. Hunter ◽  
L. J. M. van Keulen ◽  
F. Lantier ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Transmissible Spongiform Encephalopathy ◽  
Infected Sheep ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Sequence Variants ◽  
Spongiform Encephalopathies

ABSTRACTSusceptibility or resistance to prion infection in humans and animals depends on single prion protein (PrP) amino acid substitutions in the host, but the agent's modulating role has not been well investigated. Compared to disease incubation times in wild-type homozygous ARQ/ARQ (where each triplet represents the amino acids at codons 136, 154, and 171, respectively) sheep, scrapie susceptibility is reduced to near resistance in ARR/ARR animals while it is strongly enhanced in VRQ/VRQ carriers. Heterozygous ARR/VRQ animals exhibit delayed incubation periods. In bovine spongiform encephalopathy (BSE) infection, the polymorphism effect is quite different although the ARR allotype remains the least susceptible. In this study, PrP allotype composition in protease-resistant prion protein (PrPres) from brain of heterozygous ARR/VRQ scrapie-infected sheep was compared with that of BSE-infected sheep with a similar genotype. A triplex Western blotting technique was used to estimate the two allotype PrP fractions in PrPresmaterial from BSE-infected ARR/VRQ sheep. PrPresin BSE contained equimolar amounts of VRQ- and ARR-PrP, which contrasts with the excess (>95%) VRQ-PrP fraction found in PrP in scrapie. This is evidence that transmissible spongiform encephalopathy (TSE) agent properties alone, perhaps structural aspects of prions (such as PrP amino acid sequence variants and PrP conformational state), determine the polymorphic dependence of the PrPresaccumulation process in prion formation as well as the disease-associated phenotypic expressions in the host.IMPORTANCETransmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative and transmissible diseases caused by prions. Amino acid sequence variants of the prion protein (PrP) determine transmissibility in the hosts, as has been shown for classical scrapie in sheep. Each individual produces a separate PrP molecule from its two PrP gene copies. Heterozygous scrapie-infected sheep that produce two PrP variants associated with opposite scrapie susceptibilities (136V-PrP variant, high; 171R-PrP variant, very low) contain in their prion material over 95% of the 136V PrP variant. However, when these sheep are infected with prions from cattle (bovine spongiform encephalopathy [BSE]), both PrP variants occur in equal ratios. This shows that the infecting prion type determines the accumulating PrP variant ratio in the heterozygous host. While the host's PrP is considered a determining factor, these results emphasize that prion structure plays a role during host infection and that PrP variant involvement in prions of heterozygous carriers is a critical field for understanding prion formation.

scholarly journals 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

2012 ◽  
Vol 93 (7) ◽  
pp. 1624-1629 ◽  
Author(s):  
Rona Wilson ◽  
Chris Plinston ◽  
Nora Hunter ◽  
Cristina Casalone ◽  
Cristiano Corona ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Chronic Wasting Disease ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Wild Type ◽  
Wasting Disease ◽  
Spongiform Encephalopathies ◽  
Jakob Disease ◽  
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). Upon challenge with these ruminant TSEs, gene-targeted Tg mice expressing human PrP did not show any signs of disease pathology. These data strongly suggest the presence of a substantial transmission barrier between these recently identified ruminant TSEs and humans.

scholarly journals Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

2011 ◽  
Vol 42 (1) ◽  
pp. 79 ◽  
Author(s):  
Hiroyuki Okada ◽  
Yoshifumi Iwamaru ◽  
Morikazu Imamura ◽  
Kentaro Masujin ◽  
Yuichi Matsuura ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Spongiform Encephalopathy ◽  
Protein Deposits
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