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Revue Scientifique Et Technique... Jun 1992The first diagnosis of bovine spongiform encephalopathy (BSE) in the United Kingdom in 1986 was to stimulate the most intensive epidemiological study of any animal... (Review)
Review
The first diagnosis of bovine spongiform encephalopathy (BSE) in the United Kingdom in 1986 was to stimulate the most intensive epidemiological study of any animal disease of all time in that country. It led also to the initiation of a broad-based research programme with an international flavour. This principally involved scientists and veterinarians in Europe (especially the United Kingdom) and the United States of America, especially those with experience of slow infections in general and experimental scrapie in particular. This final chapter highlights some of the significant discoveries made in the study of BSE and related diseases of this group but also emphasises the deficits in knowledge which need to be corrected before such diseases as scrapie in sheep and goats can be brought under control. The benefits resultant upon effective disease control will be manifest as improvement in animal production, welfare and, importantly, the removal of trading barriers currently in place to protect countries in which diseases such as BSE and scrapie do not exist. Of key importance is the development of a simple, cheap and effective diagnostic test for use in the live animal before the onset of clinical signs. This will be difficult since the nature of the causal agents is uncertain and none provokes either a detectable immune response or inflammatory reaction in the host. The earlier chapters, written by acknowledged specialists from around the world, deal with the specific diseases in detail and all present some of the most recent knowledge available. Here the authors emphasise the important role that major national and international agencies have in effecting the highest level of control possible in the absence of key information. International collaboration with countries in which these diseases exist, and as well as those where they are absent, is of paramount importance. It is essential that the BSE epidemic which has severely affected the cattle industry of the United Kingdom is not allowed to happen in developing countries. Whereas the former has implemented stringent control measures based on scientific knowledge and is well on the way to eradicating the disease, the latter could have much greater difficulty in establishing control. The answer is clear. BSE must be prevented from occurring elsewhere. To do that, knowledge of BSE and other members of the group should be widely dispersed and it is the purpose of this issue to do just that.
Topics: Animals; Cattle; Encephalopathy, Bovine Spongiform; Goats; Humans; Scrapie; Sheep; Slow Virus Diseases; United Kingdom
PubMed: 1617204
DOI: 10.20506/rst.11.2.609 -
The Cornell Veterinarian Apr 1991
Topics: Animals; Brain Diseases; Cattle; Cattle Diseases; Goat Diseases; Goats; History, 18th Century; History, 19th Century; History, 20th Century; Prions; Scrapie; Sheep
PubMed: 2029844
DOI: No ID Found -
The Journal of General Virology Mar 2016Real-time quaking-induced conversion (RT-QuIC) is a rapid, specific and highly sensitive prion seeding activity detection assay that uses recombinant prion protein...
Real-time quaking-induced conversion (RT-QuIC) is a rapid, specific and highly sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrPSen) to detect subinfectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully used to detect PrPSc in various tissues from humans and animals, including sheep, tissues from goats infected with classical scrapie have not yet been tested. Therefore, the aims of the present study were to (1) evaluate whether prion seeding activity could be detected in the brain tissues of goats with scrapie using RT-QuIC, (2) optimize reaction conditions to improve scrapie detection in goats, and (3) compare the performance of RT-QuIC for the detection of PrPSc with the more commonly used ELISA and Western blot assays. We further optimized RT-QuIC conditions for sensitive and specific detection of goat scrapie seeding activity in brain tissue from clinical animals. When used with 200 mM sodium chloride, both full-length sheep rPrPSen substrates (PrP genotypes A136R154Q171 and V136R154Q171) provided good discrimination between scrapie-infected and normal goat brain samples at 10(- )3 dilution within 15 h. Our findings indicate that RT-QuIC was at least 10,000-fold more sensitive than ELISA and Western blot assays for the detection of scrapie seeding activity in goat brain samples. In addition to PRNP WT samples, positive RT-QuIC reactions were also observed with three PRNP polymorphic goat brain samples (G/S127, I/M142 and H/R143) tested. Taken together, these findings demonstrate that RT-QuIC sensitively detects prion seeding activity in classical scrapie-infected goat brain samples.
Topics: Animals; Biological Assay; Brain; Goat Diseases; Goats; PrPC Proteins; PrPSc Proteins; Scrapie; Sensitivity and Specificity
PubMed: 26653410
DOI: 10.1099/jgv.0.000367 -
BMC Veterinary Research Feb 2009In the wake of the epidemic of bovine spongiform encephalopathy the British government established a flock of sheep from which scrapie-free animals are supplied to...
BACKGROUND
In the wake of the epidemic of bovine spongiform encephalopathy the British government established a flock of sheep from which scrapie-free animals are supplied to laboratories for research. Three breeds of sheep carrying a variety of different genotypes associated with scrapie susceptibility/resistance were imported in 1998 and 2001 from New Zealand, a country regarded as free from scrapie. They are kept in a purpose-built Sheep Unit under strict disease security and are monitored clinically and post mortem for evidence of scrapie. It is emphasised that atypical scrapie, as distinct from classical scrapie, has been recognised only relatively recently and differs from classical scrapie in its clinical, neuropathological and biochemical features. Most cases are detected in apparently healthy sheep by post mortem examination.
RESULTS
The occurrence of atypical scrapie in three sheep in (or derived from) the Sheep Unit is reported. Significant features of the affected sheep included their relatively high ages (6 y 1 mo, 7 y 9 mo, 9 y 7 mo respectively), their breed (all Cheviots) and their similar PRNP genotypes (AFRQ/AFRQ, AFRQ/ALRQ, and AFRQ/AFRQ, respectively). Two of the three sheep showed no clinical signs prior to death but all were confirmed as having atypical scrapie by immunohistochemistry and Western immunoblotting. Results of epidemiological investigations are presented and possible aetiologies of the cases are discussed.
CONCLUSION
By process of exclusion, a likely explanation for the three cases of atypical scrapie is that they arose spontaneously and were not infected from an exterior source. If correct, this raises challenging issues for countries which are currently regarded as free from scrapie. It would mean that atypical scrapie is liable to occur in flocks worldwide, especially in older sheep of susceptible genotypes. To state confidently that both the classical and atypical forms of scrapie are absent from a population it is necessary for active surveillance to have taken place.
Topics: Animals; Blotting, Western; Brain; Genotype; Immunohistochemistry; Prions; Scrapie; Sheep; United Kingdom
PubMed: 19208228
DOI: 10.1186/1746-6148-5-8 -
BMC Veterinary Research Sep 2018Incubation period, disease progression, pathology and clinical presentation of classical scrapie in sheep are highly dependent on PRNP genotype, time and route of...
Expression of selected genes isolated from whole blood, liver and obex in lambs with experimental classical scrapie and healthy controls, showing a systemic innate immune response at the clinical end-stage.
BACKGROUND
Incubation period, disease progression, pathology and clinical presentation of classical scrapie in sheep are highly dependent on PRNP genotype, time and route of inoculation and prion strain. Our experimental model with pre-colostrum inoculation of homozygous VRQ lambs has shown to be an effective model with extensive PrP dissemination in lymphatic tissue and a short incubation period with severe clinical disease. Serum protein analysis has shown an elevation of acute phase proteins in the clinical stages of this experimental model, and here, we investigate changes in gene expression in whole blood, liver and brain.
RESULTS
The animals in the scrapie group showed severe signs of illness 22 weeks post inoculation necessitating euthanasia at 23 weeks post inoculation. This severe clinical presentation was accompanied by changes in expression of several genes. The following genes were differentially expressed in whole blood: TLR2, TLR4, C3, IL1B, LF and SAA, in liver tissue, the following genes differentially expressed: TNF-α, SAA, HP, CP, AAT, TTR and TF, and in the brain tissue, the following genes were differentially expressed: HP, CP, ALB and TTR.
CONCLUSIONS
We report a strong and evident transcriptional innate immune response in the terminal stage of classical scrapie in these animals. The PRNP genotype and time of inoculation are believed to contribute to the clinical presentation, including the extensive dissemination of PrP throughout the lymphatic tissue.
Topics: Animals; Animals, Newborn; Blood; Brain; Gene Expression Profiling; Genotype; Immunity, Innate; Liver; PrPSc Proteins; Scrapie; Sheep, Domestic
PubMed: 30208891
DOI: 10.1186/s12917-018-1607-9 -
Veterinary Research 2009The susceptibility of sheep to scrapie is under the control of the host's prion protein (PrP gene and is also influenced by the strain of the agent. PrP polymorphisms at...
The susceptibility of sheep to scrapie is under the control of the host's prion protein (PrP gene and is also influenced by the strain of the agent. PrP polymorphisms at codons 136 (A/V), 15 (R/H) and 171 (Q/R/H) are the main determinants of susceptibility/resistance of sheep to classical scrapie. They are combined in four main variants of the wild-type ARQ allele: VRQ, AHQ, ARH and ARR. Breeding programmes have been undertaken on this basis in the European Union and th USA to increase the frequency of the resistant ARR allele in sheep populations. Herein, we report th results of a multi-flock study showing the protective effect of polymorphisms other than those a codons 136, 154 and 171 in Sarda breed sheep. All ARQ/ARQ affected sheep (n = 154) and 37 negative ARQ/ARQ controls from four scrapie outbreaks were submitted to sequencing of the Pr gene. The distribution of variations other than those at the standard three codons, between scrapie cases and negative controls, was statistically different in all flocks. In particular, the AT(137)RQ an ARQK(176) alleles showed a clear protective effect. This is the first study demonstrating a protective influence of alleles other than ARR under field conditions. If further investigations in other sheep breeds and with other scrapie sources confirm these findings, the availability of various protective alleles in breeding programmes of sheep for scrapie resistance could be useful in breeds with a low frequency of the ARR allele and would allow maintaining a wider variability of the PrP gene.
Topics: Alleles; Animals; Disease Outbreaks; Genetic Predisposition to Disease; Genotype; Italy; Scrapie; Sheep
PubMed: 19171116
DOI: 10.1051/vetres/2009002 -
Comptes Rendus Biologies Jan 2002Sheep scrapie is a prototypical transmissible spongiform encephalopathy (TSE), and the most widespread of these diseases. Experimental study of TSE infectious agents... (Review)
Review
Sheep scrapie is a prototypical transmissible spongiform encephalopathy (TSE), and the most widespread of these diseases. Experimental study of TSE infectious agents from sheep and other species essentially depends on bioassays in rodents. Transmission of natural sheep scrapie to conventional mice commonly requires one or two years. In an effort to develop laboratory models in which investigations on the sheep TSE agent would be facilitated, we have established mice and cell lines that were genetically engineered to express ovine PrP protein and examined their susceptibility to the infection. A series of transgenic mice lines (tgOv) expressing the high susceptibility allele (VRQ) of the ovine PrP gene from different constructs was expanded. Following intracerebral inoculation with natural scrapie isolates, all animals developed typical TSE neurological signs and accumulated abnormal PrP in their brain. The survival time in the highest expressing tgOv lines ranged from 2 to 7 months, depending on the isolate. It was inversely related to the brain PrP content, and essentially unchanged on further passaging. Ovine PrP transgene expression thus enhanced scrapie disease transmission from sheep to mice. Such tgOv mice may bring new opportunities for analysing the natural variation of scrapie strains and measuring infectivity. As no relevant cell culture models for agents of naturally-occurring TSE exist, we have explored various strategies in order to obtain stable cell lines that would propagate the sheep agent ex vivo without prior adaptation to rodent. In one otherwise refractory rabbit epithelial cell line, a regulable expression of ovine PrP was achieved and found to enable an efficient replication of the scrapie agent in inoculated cultures. Cells derived from sheep embryos or from tgOv mice were also used in an attempt to establish permissive cell lines derived from the nervous system. Cells engineered to express PrP proteins of a specified sequence may thus represent a promising strategy to further explore, at the cellular level, various aspects of TSE diseases.
Topics: Alleles; Animals; Cell Line; Disease Models, Animal; Gene Expression; Genetic Predisposition to Disease; Mice; Mice, Transgenic; Prions; Scrapie; Sheep
PubMed: 11862622
DOI: 10.1016/s1631-0691(02)01393-8 -
Genes Sep 2021Selection based on scrapie genotypes could improve the genetic resistance for scrapie in sheep. However, in practice, few animals are genotyped. The objectives were to...
Selection based on scrapie genotypes could improve the genetic resistance for scrapie in sheep. However, in practice, few animals are genotyped. The objectives were to define numerical values of scrapie resistance genotypes and adjust for their non-additive genetic effect; evaluate prediction accuracy of ungenotyped animals using linear animal model; and predict and assess selection response based on estimated breeding values (EBV) of ungenotyped animals. The scrapie resistance (SR) was defined by ranking scrapie genotypes from low (0) to high (4) resistance based on genotype risk groups and was also adjusted for non-additive genetic effect of the haplotypes. Genotypes were simulated for 1,671,890 animals from pedigree. The simulated alleles were assigned to scrapie haplotypes in two scenarios of high (SR) and low (SR) resistance populations. A sample of 20,000 genotyped animals were used to predict ungenotyped using animal model. Prediction accuracies for ungenotyped animals for SR and SR were 0.60 and 0.54, and for allele content were from 0.41 to 0.71, respectively. Response to selection on SR and SR increased SR by 0.52 and 0.28, and on allele content from 0.13 to 0.50, respectively. In addition, the selected animals had large proportion of homozygous for the favorable haplotypes. Thus, pre-selection prior to genotyping could reduce genotyping costs for breeding programs. Using a linear animal model to predict SR makes better use of available information for the breeding programs.
Topics: Animals; Breeding; Computer Simulation; Disease Resistance; Genotype; Haplotypes; Models, Animal; Pedigree; Phenotype; Prognosis; Scrapie; Selection, Genetic; Sheep
PubMed: 34573414
DOI: 10.3390/genes12091432 -
BMC Veterinary Research Sep 2009Previous studies suggest that the spatial distribution of classical sheep scrapie in Great Britain is uneven and that certain flock characteristics may be associated...
BACKGROUND
Previous studies suggest that the spatial distribution of classical sheep scrapie in Great Britain is uneven and that certain flock characteristics may be associated with occurrence of the disease. However, the existence of areas of high and low disease-risk may also result from differences in the spatial distribution of environmental characteristics. In this study we explored the spatial pattern of classical scrapie in Great Britain between 2002 and 2005 and investigated the association between disease occurrence and various environmental and farm-related risk factors.
RESULTS
Exploratory spatial analysis: South Wales was found to have a higher density of scrapie-positive farms than the rest of Great Britain. In addition, a small cluster of high-risk farms was identified in the center of this region in which clustering of scrapie-positive farms occurred up to a distance of approximately 40 km. SPATIAL MODELLING: A mixed-effects regression model identified flock-size and soil drainage to be significantly associated with the occurrence of scrapie in England and Wales (area under the curve (AUC) 0.71 +/- 0.01, 95% CI 0.68 - 0.74). The predictive risk map based on the estimated association between these factors and disease occurrence showed most of Wales to be at risk of being confirmed positive for scrapie with areas of highest risk in central and south Wales. In England, areas with the highest risk occurred mainly in the north and the midlands.
CONCLUSION
The observed distribution of scrapie in Great Britain exhibited a definite spatial pattern with south Wales identified as an area of high occurrence. In addition both flock (flock size) and environmental variables (soil drainage) were found to be significantly associated with the occurrence of the disease. However, the model's AUC indicated unexplained variation remaining in the model and the source of this variation may lie in farm-level characteristics rather than spatially-varying ones such as environmental factors.
Topics: Animal Husbandry; Animals; Demography; Environment; Models, Biological; Risk Factors; Scrapie; Sheep; United Kingdom
PubMed: 19737376
DOI: 10.1186/1746-6148-5-33 -
Veterinary Research Apr 2021The diversity of goat scrapie strains in Europe has recently been studied using bioassays in a wide collection of rodent models, resulting in the classification of...
The diversity of goat scrapie strains in Europe has recently been studied using bioassays in a wide collection of rodent models, resulting in the classification of classical scrapie into four different categories. However, the sole use of the first passage does not lead to isolate adaptation and identification of the strains involved and might therefore lead to misclassification of some scrapie isolates. Therefore, this work reports the complete transmission study of a wide collection of goat transmissible spongiform encephalopathy (TSE) isolates by intracranial inoculation in two transgenic mouse lines overexpressing either small ruminant (TgGoat-ARQ) or bovine (TgBov) PrP. To compare scrapie strains in sheep and goats, sheep scrapie isolates from different European countries were also included in the study. Once the species barrier phenomenon was overcome, an accurate classification of the isolates was attained. Thus, the use of just two rodent models allowed us to fully differentiate at least four different classical scrapie strains in small ruminants and to identify isolates containing mixtures of strains. This work reinforces the idea that classical scrapie in small ruminants is a prion disease caused by multiple different prion strains and not by a single strain, as is the case for epidemic classical bovine spongiform encephalopathy (BSE-C). In addition, the clear dissimilarity between the different scrapie strains and BSE-C does not support the idea that classical scrapie is the origin of epidemic BSE-C.
Topics: Animals; Europe; Goat Diseases; Goats; Prions; Scrapie; Sheep; Sheep Diseases; Sheep, Domestic
PubMed: 33858518
DOI: 10.1186/s13567-021-00929-7