scholarly journals Ovine prion protein variant A136R154L168Q171 increases resistance to experimental challenge with bovine spongiform encephalopathy agent

2006 ◽  
Vol 87 (12) ◽  
pp. 3741-3745 ◽  
Author(s):  
Wilfred Goldmann ◽  
Fiona Houston ◽  
Paula Stewart ◽  
Matteo Perucchini ◽  
James Foster ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Protein Variant ◽  
Spongiform Encephalopathies ◽  
The Standard Model ◽  
Incubation Periods ◽  
Prp Gene ◽  
Bovine Spongiform Encephalopathy Agent ◽  
Experimental Challenge

Susceptibility and incubation periods of transmissible spongiform encephalopathies, such as scrapie in sheep, are modulated by the PrP gene. The standard model of association between ovine PrP genetics and classical scrapie susceptibility is based on PrP genotypes with respect to codons 136, 154 and 171, e.g. alanine–arginine–glutamine (ARQ). It is demonstrated here that a proline to leucine substitution in codon 168 of the ovine PrP protein gene is associated with increased resistance to experimental bovine spongiform encephalopathy (BSE) inoculation. The ARL168Q PrP allele was found in heterozygous ARP168Q/ARL168Q sheep that have so far survived intravenous BSE challenge three times longer than BSE-challenged homozygous ARP168Q/ARP168Q sheep, which develop disease in around 700 days. In contrast, the L141F polymorphism does not appear to be associated with susceptibility to intravenous BSE challenge.

scholarly journals Bovine spongiform encephalopathy agent in spleen from an ARR/ARR orally exposed sheep

2006 ◽  
Vol 87 (4) ◽  
pp. 1043-1046 ◽  
Author(s):  
Olivier Andréoletti ◽  
Nathalie Morel ◽  
Caroline Lacroux ◽  
Virginie Rouillon ◽  
Céline Barc ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Food Chain ◽  
Small Ruminant ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Spongiform Encephalopathies ◽  
Widespread Distribution ◽  
Prnp Genotype ◽  
Human Food Chain ◽  
Bovine Spongiform Encephalopathy Agent

Oral contamination with bovine spongiform encephalopathy (BSE) agent in susceptible PRNP genotype sheep results in widespread distribution of prion in the host. Because ARR homozygous sheep are considered to be resistant to transmissible spongiform encephalopathies, they have been selected to eradicate scrapie from sheep flocks and to protect the human food chain from small ruminant BSE risk. However, results presented here show that several months after an oral challenge with BSE agent, healthy ARR/ARR sheep can accumulate significant amounts of PrPSc in the spleen.

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.

Are Bacterial Toxins Involved in the Aetiology of Transmissible Spongiform Encephalopathies?

1997 ◽  
Vol 11 (4) ◽  
pp. 301-307 ◽  
Author(s):  
T. Stockdale
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Bacterial Toxins ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Meat And Bone Meal ◽  
Bone Meal ◽  
Spongiform Encephalopathies ◽  
Infected Meat ◽  
Disease Epidemics ◽  
The Brain

It is argued that the conditions for Bovine Spongiform Encephalopathy and Creutzfeld-Jacob disease epidemics necessitate, in addition to a diet that contains infected meat and bone meal, the presence of leaky membranes that enable bacterial toxins to circulate in the blood and enter the brain.

Use of 14-3-3 in the diagnosis of Creutzfeldt-Jakob disease

2002 ◽  
Vol 30 (4) ◽  
pp. 382-386 ◽  
Author(s):  
A. J. E. Green
Keyword(s):  
Cerebrospinal Fluid ◽  
Bovine Spongiform Encephalopathy ◽  
Diagnostic Tests ◽  
Human Diseases ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Spongiform Encephalopathies ◽  
Animal Diseases ◽  
Jakob Disease ◽  
Sporadic Cjd

The transmissible spongiform encephalopathies include human diseases such as Creutzfeldt-Jakob disease (CJD) and kuru as well as animal diseases such as scrapie and bovine spongiform encephalopathy (BSE). The emergence of variant CJD, which is causally related to BSE, has generated much interest in the development of rapid and sensitive diagnostic tests for the pre-mortem diagnosis of CJD. In 1986 two proteins were detected in the cerebrospinal fluid (CSF) of patients with sporadic CJD. These proteins were later demonstrated to be members of the 14-3-3 family, and tests for the detection of CSF 14-3-3 were developed. A number of studies have shown that the detection of CSF 14-3-3 is an accurate test for sporadic CJD, although the results with variant CJD are less promising.

scholarly journals Autoantibodies to Brain Components and Antibodies to Acinetobacter calcoaceticus Are Present in Bovine Spongiform Encephalopathy

1999 ◽  
Vol 67 (12) ◽  
pp. 6591-6595 ◽  
Author(s):  
Harmale Tiwana ◽  
Clyde Wilson ◽  
John Pirt ◽  
William Cartmell ◽  
Alan Ebringer
Keyword(s):  
Escherichia Coli ◽  
Bovine Spongiform Encephalopathy ◽  
Immunoglobulin A ◽  
Acinetobacter Calcoaceticus ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Allergic Encephalomyelitis ◽  
Spongiform Encephalopathies ◽  
Jakob Disease ◽  
Experimental Allergic

ABSTRACT Bovine spongiform encephalopathy (BSE) is a neurological disorder, predominantly of British cattle, which belongs to the group of transmissible spongiform encephalopathies together with Creutzfeldt-Jakob disease (CJD), kuru, and scrapie. Autoantibodies to brain neurofilaments have been previously described in patients with CJD and kuru and in sheep affected by scrapie. Spongiform-like changes have also been observed in chronic experimental allergic encephalomyelitis, at least in rabbits and guinea pigs, and in these conditions autoantibodies to myelin occur. We report here that animals with BSE have elevated levels of immunoglobulin A autoantibodies to brain components, i.e., neurofilaments (P < 0.001) and myelin (P < 0.001), as well as toAcinetobacter calcoaceticus (P < 0.001), saprophytic microbes found in soil which have sequences cross-reacting with bovine neurofilaments and myelin, but there were no antibody elevations against Agrobacterium tumefaciens orEscherichia coli. The relevance of such mucosal autoantibodies or antibacterial antibodies to the pathology of BSE and its possible link to prions requires further evaluation.

scholarly journals Prion disease: advances in diagnosis and treatment

2005 ◽  
Vol 4 (10) ◽  
pp. 273-278
Author(s):  
Steve Dealler
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Disease ◽  
Transmissible Spongiform Encephalopathies ◽  
The Political ◽  
Spongiform Encephalopathy ◽  
Potential Treatment ◽  
Spongiform Encephalopathies ◽  
Current State ◽  
Jakob Disease ◽  
Pentosan Polysulphate

Steve Dealler is a medical microbiologist with Morecambe Bay Hospitals NHS Trust. His work on on the diagnosis, epidemiology and potential treatment of transmissible spongiform encephalopathies has brought him inter-national recognition. He has been at the forefront of work on the epidemiology of human food containing the vector for bovine spongiform encephalopathy (BSE), and the development of prophylaxis against variant Creutzfeldt-Jakob disease (vCJD). He is currently working on a potential treatment, pentosan polysulphate. Here he describes the current state of knowledge in the battle against this devastating disease and the political inertia that frustrated earlier attempts to prevent the epidemic.

scholarly journals PrPTSE in muscle-associated lymphatic tissue during the preclinical stage of mice infected orally with bovine spongiform encephalopathy

2009 ◽  
Vol 90 (10) ◽  
pp. 2563-2568 ◽  
Author(s):  
Franco Cardone ◽  
Achim Thomzig ◽  
Walter Schulz-Schaeffer ◽  
Angelina Valanzano ◽  
Marco Sbriccoli ◽  
...  
Keyword(s):  
Nervous System ◽  
Bovine Spongiform Encephalopathy ◽  
Neuromuscular Junctions ◽  
Clinical Stage ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Muscle Fibres ◽  
Preclinical Stage ◽  
Spongiform Encephalopathies ◽  
Stage Of Disease

The involvement of muscles in the pathogenesis of transmissible spongiform encephalopathies (TSEs) is irregular and unpredictable. We show that the TSE-specific protein (PrPTSE) is present in muscles of mice fed with a mouse-adapted strain of bovine spongiform encephalopathy as early as 100 days post-infection, corresponding to about one-third of the incubation period. The proportion of mice with PrPTSE-positive muscles and the number of muscles involved increased as infection progressed, but never attained more than a limited distribution, even at the clinical stage of disease. The appearance of PrPTSE in muscles during the preclinical stage of disease was probably due to the haematogenous/lymphatic spread of infectivity from the gastrointestinal tract to lymphatic tissues associated with muscles, whereas in symptomatic animals, the presence of PrPTSE in the nervous system, in neuromuscular junctions and in muscle fibres suggests a centrifugal spread from the central nervous system, as already observed in other TSE models.

scholarly journals Transmission and characterization of bovine spongiform encephalopathy sources in two ovine transgenic mouse lines (TgOvPrP4 and TgOvPrP59)

2006 ◽  
Vol 87 (12) ◽  
pp. 3763-3771 ◽  
Author(s):  
C. Cordier ◽  
A. Bencsik ◽  
S. Philippe ◽  
D. Bétemps ◽  
F. Ronzon ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Bovine Spongiform Encephalopathy ◽  
Transgenic Mouse ◽  
Neuron Specific Enolase ◽  
Infected Sheep ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Wild Type ◽  
Spongiform Encephalopathies ◽  
Mouse Lines

Transgenic mice expressing the prion protein (PrP) of species affected by transmissible spongiform encephalopathies (TSEs) have recently been produced to facilitate experimental transmission of these diseases by comparison with wild-type mice. However, whilst wild-type mice have largely been described for the discrimination of different TSE strains, including differentiation of agents involved in bovine spongiform encephalopathy (BSE) and scrapie, this has been only poorly described in transgenic mice. Here, two ovine transgenic mouse lines (TgOvPrP4 and TgOvPrP59), expressing the ovine PrP (A136 R154 Q171) under control of the neuron-specific enolase promoter, were studied; they were challenged with brainstem or spinal cord from experimentally BSE-infected sheep (AA136 RR154 QQ171 and AA136 RR154 RR171 genotypes) or brainstem from cattle BSE and natural sheep scrapie. The disease was transmitted successfully from all of these sources, with a mean of approximately 300 days survival following challenge with material from two ARQ-homozygous BSE-infected sheep in TgOvPrP4 mice, whereas the survival period in mice challenged with material from the ARR-homozygous BSE-infected sheep was 423 days on average. It was shown that, in the two ovine transgenic mouse lines, the Western blot characteristics of protease-resistant PrP (PrPres) were similar, whatever the BSE source, with a low apparent molecular mass of the unglycosylated glycoform, a poor labelling by P4 monoclonal antibody and high proportions of the diglycosylated form. With all BSE sources, but not with scrapie, florid plaques were observed in the brains of mice from both transgenic lines. These data reinforce the potential of this recently developed experimental model for the discrimination of BSE from scrapie agents.

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