Search Results (13)

Scrapie (classical and atypical) susceptibility in sheep is strongly influenced by PRNP gene polymorphisms. In Portugal, limited data exist for native breeds such as Serra da Estrela, despite their relevance to animal conservation and food production. The full coding region of PRNP gene of 92 Serra da Estrela sheep was sequenced and SNP frequencies were analysed. The predicted functional impact of nonsynonymous SNPs was assessed using PolyPhen-2 and AMYCO. A total of 27 SNPs were identified, including 20 nonsynonymous variants. Thirteen major haplotypes were observed. The ARR allele, which provides resistance to classical scrapie, was present in 58.7% of the population, with 18.5% of animals being homozygous. Several previously unreported SNPs were identified, and their impact on prion protein aggregation propensity and structure was explored. The high frequency of the ARR allele without full ARR fixation suggests that no selective breeding for scrapie resistance has been applied. These results support the adoption of gradual selection strategies that preserve genetic variability and promote farmer compliance, while increasing classical and atypical scrapie resistance. Full article

Scrapie is a notifiable transmissible spongiform encephalopathy (TSE) in sheep that relies on clinical examinations for reporting suspects. A short examination protocol was used in 1002 sheep to define clinical markers suggestive of scrapie. Sheep were naturally or experimentally exposed to a classical, atypical scrapie or bovine spongiform encephalopathy agent; 312 were positive for a transmissible spongiform encephalopathy (TSE) by brain examination and included non-exposed controls. Assessed signs were posture, behaviour, menace, scratch and blindfolding response, wool loss and skin changes, body condition, incoordination and tremor. First, the combined occurrence of two or more clinical signs was compared between TSE-positive and negative sheep. Second, the importance of clinical markers was determined in a general classification and regression tree model. The main clinical markers to predict TSEs according to the tree model were incoordination and a positive scratch test. Test sensitivities and specificities were 70.8–81.5% and 96.1–93.0%, respectively, and predictive values above 87%. The results suggest that the short clinical protocol, which assesses the presence of certain clinical signs associated with a TSE in sheep and is quick to perform, may be useful to reach a suspect diagnosis in both naturally and experimentally generated TSEs. Full article

Atypical scrapie (AS) is a transmissible spongiform encephalopathy (TSE) that affects sheep and goats. Low within-flock incidence suggests that AS is not transmissible between animals, and testing of all animals that exit positive flocks for two years following detection (i.e., intensified monitoring) used to be carried out in the EU to provide data to test this. This intensified monitoring stopped in 2021 but continues in Great Britain (GB). The aim of this study was to predict the number of AS cases missed if this monitoring were also stopped in GB, using a combination of statistical and transmission modelling. The number of AS cases estimated to be missed if the intensified monitoring was stopped was low relative to the number of AS cases detected in other active surveillance streams (e.g., fallen stock and abattoir surveys), at approximately 1 case every 3 years (0.34 per year, 95% CI: 0.18–0.54) compared to 10 per year (95% CI: 4–17) in the active surveillance stream. This suggests that stopping the intensive monitoring of AS would have relatively little impact on AS surveillance and on the power of the available AS data to infer whether AS is contagious. Full article

After the detection of bovine spongiform encephalopathy (BSE), and a zoonotic transmissible spongiform encephalopathy (TSE) caused by the pathological prion protein (PrP^Sc) in two goats, the investigation of goat prions became of greater interest. Therefore, a broad collection of European goat TSE isolates, including atypical scrapie, CH1641 and goat BSE as reference prion strains were biochemically characterised and subsequently inoculated into seven rodent models for further analysis (already published results of this comprehensive study are reviewed here for comparative reasons). We report here the histopathological and immunohistochemical data of this goat TSE panel, obtained after the first passage in Tgshp IX (tg-shARQ) mice, which overexpress the ovine prion protein. In addition to the clear-cut discrimination of all reference prion strains from the classical scrapie (CS) isolates, we were further able to determine three categories of CS strains. The investigation further indicates the occurrence of sub-strains that slightly resemble distant TSE strains, such as BSE or CH1641, reinforcing the theory that CS is not a single strain but a mixture of sub-strains, existing at varying extents in one isolate. This study further proved that Tgshp IX is a potent and reliable tool for the in-depth characterisation of prion strains. Full article

Scrapie, a naturally occurring prion disease affecting goats and sheep, comprises classical and atypical forms, with classical scrapie being the archetype of transmissible spongiform encephalopathies. This review explores the challenges of scrapie diagnosis and the utility of various biomarkers and their potential implications for human prion diseases. Understanding these biomarkers in the context of scrapie may enable earlier prion disease diagnosis in humans, which is crucial for effective intervention. Research on scrapie biomarkers bridges the gap between veterinary and human medicine, offering hope for the early detection and improved management of prion diseases. Full article

Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disease that belongs to a group of diseases known as transmissible spongiform encephalopathies (TSEs). It is believed that the infectious agent responsible for prion diseases is abnormally folded prion protein (PrP^Sc), which derives from a normal cellular protein (PrP^C), which is a cell surface glycoprotein predominantly expressed in neurons. There are three different types of BSE, the classical BSE (C-type) strain and two atypical strains (H-type and L-type). BSE is primarily a disease of cattle; however, sheep and goats also can be infected with BSE strains and develop a disease clinically and pathogenically indistinguishable from scrapie. Therefore, TSE cases in cattle and small ruminants require discriminatory testing to determine whether the TSE is BSE or scrapie and to discriminate classical BSE from the atypical H- or L-type strains. Many methods have been developed for the detection of BSE and have been reported in numerous studies. Detection of BSE is mainly based on the identification of characteristic lesions or detection of the PrP^Sc in the brain, often by use of their partial proteinase K resistance properties. The objective of this paper was to summarize the currently available methods, highlight their diagnostic performance, and emphasize the advantages and drawbacks of the application of individual tests. Full article

Transmissible spongiform encephalopathies (TSE), caused by abnormal prion protein (PrP^Sc), affect many species. The most classical scrapie isolates harbor mixtures of strains in different proportions. While the characterization of isolates has evolved from using wild-type mice to transgenic mice, no standardization is established yet. Here, we investigated the incubation period, lesion profile and PrP^Sc profile induced by well-defined sheep scrapie isolates, bovine spongiform encephalopathy (BSE) and ovine BSE after intracerebral inoculation into two lines of ovine PrP (both ARQ/ARQ) overexpressing transgenic mice (Tgshp IX and Tgshp XI). All isolates were transmitted to both mouse models with an attack rate of almost 100%, but genotype-dependent differences became obvious between the ARQ and VRQ isolates. Surprisingly, BSE induced a much longer incubation period in Tgshp XI compared to Tgshp IX. In contrast to the histopathological lesion profiles, the immunohistochemical PrP^Sc profiles revealed discriminating patterns in certain brain regions in both models with clear differentiation of both BSE isolates from scrapie. These data provide the basis for the use of Tgshp IX and XI mice in the characterization of TSE isolates. Furthermore, the results enable a deeper appreciation of TSE strain diversity using ovine PrP overexpressing transgenic mice as a biological prion strain typing approach. Full article

Naturally occurring neuron-abundant proteins including amyloid Aβ42 peptide and the microtubule-associated protein tau (MAPT) can, over time and under pathological situations, assume atypical conformations, altering their normal biological structure and function, and causing them to aggregate into insoluble and neurotoxic intracellular inclusions. These misfolded proteins ultimately contribute to the pathogenesis of several progressive, age-related and ultimately lethal human neurodegenerative disorders. The molecular mechanism of this pathological phenomenon of neuronal protein misfolding lends support to the ‘prion hypothesis’, which predicts that the aberrant folding of endogenous natural protein structures into unusual pathogenic isoforms can induce the atypical folding of other similar brain-abundant proteins, underscoring the age-related, progressive nature and potential transmissible and spreading capabilities of the aberrant protein isoforms that drive these invariably fatal neurological syndromes. The abnormal folding and aggregation of host proteins is a consistent feature of both amyloidopathies and tauopathies that encompass a continuous spectrum of brain diseases that include Alzheimer’s disease (AD), prion disorders (PrD) such as scrapie in sheep and goats (Bovidae), experimental prion infection of rodents (Muridae), Creutzfeldt–Jakob disease (CJD) and Gerstmann–Sträussler–Scheinker syndrome (GSS) in humans (Hominidae), and other fatal prion-driven neurological disorders. Because AD patients accumulate both misfolded tau and Aβ peptides, AD may be somewhat unique as the first example of a ‘double prion disorder’. This commentary will examine current research trends in this fascinating research area, with a special emphasis on AD and PrD, and the novel pathological misfolded protein processes common to both intractable neurological disorders. Full article

Wasting disease in small ruminants is frequently detected at slaughterhouses. The wasting disorder is manifested by the deterioration of the nutritional and physiological state of the animal indicated by thinness, emaciation, and cachexia. Evidence of emaciation and cachexia, alone, are pathological conditions leading to carcass condemnation during an inspection. Several diseases are associated with a wasting condition, including scrapie, pseudotuberculosis, tuberculosis, paratuberculosis, Maedi Visna, and tumor diseases. On the other hand, parasitic diseases, nutrition disorders, exposure or ingestion of toxins, metabolic conditions, inadequate nutrition due to poor teeth, or poor alimentary diet are conditions contributing to poor body condition. Classical and atypical scrapie is naturally occurring transmissible spongiform encephalopathies in small ruminants. The etiological agent for each one is prions. However, each of these scrapie types is epidemiologically, pathologically, and biochemically different. Though atypical scrapie occurs at low incidence, it is consistently prevalent in the small ruminant population. Hence, it is advisable to include differential diagnosis of this disease, from other possibilities, as a cause of wasting conditions detected during meat inspection at the abattoir. This manuscript is a review of the measures in force at the abattoir for scrapie control, focusing on the differential diagnosis of gross lesions related to wasting conditions detected in small ruminants during meat inspection. Full article

Portugal was among the first European countries to report cases of Atypical Scrapie (ASc), the dominant form of Transmissible Spongiform Encephalopathy (TSE) in Portuguese small ruminants. Although the diagnostic phenotypes observed in Portuguese ASc cases seem identical to those described for Nor98, unequivocal identification requires TSE strain-typing using murine bioassays. In this regard, we initiated characterization of ASc isolates from sheep either homozygous for the ARQ genotype or the classical scrapie-resistant ARR genotype. Isolates from such genotypes were transmitted to TgshpXI mice expressing ovine PrPARQ. Mean incubation periods were 414 ± 58 and 483 ± 107 days in mice inoculated with AL₁₄₁RQ/AF₁₄₁RQ and AL₁₄₁RR/AL₁₄₁RR sheep isolates, respectively. Both isolates produced lesion profiles similar to French ASc Nor98 ‘discordant cases’, where vacuolation was observed in the hippocampus (G6), cerebral cortex at the thalamus (G8) level, cerebellar white matter (W1) and cerebral peduncles (W3). Immunohistochemical PrP^Sc deposition was observed in the hippocampus, cerebellar cortex, cerebellar white matter and cerebral peduncles in the form of aggregates and fine granules. These findings were consistent with previously reported cases of ASc Nor98 transmitted to transgenic TgshpXI mice, confirming that the ASc strain present in Portuguese sheep corresponds to ASc Nor98. Full article

Transmissible Spongiform Encephalopathies (TSEs) or prion diseases are a fatal group of infectious, inherited and spontaneous neurodegenerative diseases affecting human and animals. They are caused by the conversion of cellular prion protein (PrP^C) into a misfolded pathological isoform (PrP^Sc or prion- proteinaceous infectious particle) that self-propagates by conformational conversion of PrP^C. Yet by an unknown mechanism, PrP^C can fold into different PrP^Sc conformers that may result in different prion strains that display specific disease phenotype (incubation time, clinical signs and lesion profile). Although the pathways for neurodegeneration as well as the involvement of brain inflammation in these diseases are not well understood, the spongiform changes, neuronal loss, gliosis and accumulation of PrP^Sc are the characteristic neuropathological lesions. Scrapie affecting small ruminants was the first identified TSE and has been considered the archetype of prion diseases, though atypical and new animal prion diseases continue to emerge highlighting the importance to investigate the lesion profile in naturally affected animals. In this report, we review the neuropathology and the neuroinflammation of animal prion diseases in natural hosts from scrapie, going through the zoonotic bovine spongiform encephalopathy (BSE), the chronic wasting disease (CWD) to the newly identified camel prion disease (CPD). Full article

Prion diseases, such as scrapie, are neurodegenerative diseases with a fatal outcome, caused by a conformational change of the cellular prion protein (PrP^C), originating with the pathogenic form (PrP^Sc). Classical scrapie in small ruminants is the paradigm of prion diseases, as it was the first transmissible spongiform encephalopathy (TSE) described and is the most studied. It is necessary to understand the etiological properties, the relevance of the transmission pathways, the infectivity of the tissues, and how we can improve the detection of the prion protein to encourage detection of the disease. The aim of this review is to perform an overview of classical and atypical scrapie disease in sheep and goats, detailing those special issues of the disease, such as genetic factors, diagnostic procedures, and surveillance approaches carried out in the European Union with the objective of controlling the dissemination of scrapie disease. Full article

Prions are an enigma amongst infectious disease agents as they lack a genome yet confer specific pathologies thought to be dictated mainly, if not solely, by the conformation of the disease form of the prion protein (PrP^Sc). Prion diseases affect humans and animals, the latter including the food-producing ruminant species cattle, sheep, goats and deer. Importantly, it has been shown that the disease agent of bovine spongiform encephalopathy (BSE) is zoonotic, causing variant Creutzfeldt Jakob disease (vCJD) in humans. Current diagnostic tests can distinguish different prion types and in food-producing animals these focus on the differentiation of BSE from the non-zoonotic agents. Whilst BSE cases are now rare, atypical forms of both scrapie and BSE have been reported, as well as two types of chronic wasting disease (CWD) in cervids. Typing of animal prion isolates remains an important aspect of prion diagnosis and is now becoming more focused on identifying the range of prion types that are present in food-producing animals and also developing tests that can screen for emerging, novel prion diseases. Here, we review prion typing methodologies in light of current and emerging prion types in food-producing animals. Full article