Characterisation of European Field Goat Prion Isolates in Ovine PrP Overexpressing Transgenic Mice (Tgshp IX) Reveals Distinct Prion Strains.

After the detection of bovine spongiform encephalopathy (BSE), and a zoonotic transmissible spongiform encephalopathy (TSE) caused by the pathological prion protein (PrP) 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.

Diagnosis in Scrapie: Conventional Methods and New Biomarkers.

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.

Novel polymorphisms in the prion protein gene (PRNP) and stability of the resultant prion protein in different horse breeds.

Prion diseases are fatal neurodegenerative disorders in which the main pathogenic event is the conversion of the cellular prion protein (PrP) into an abnormal and misfolded isoform known as PrP. Most prion diseases and their susceptibility and pathogenesis are mainly modulated by the PRNP gene that codes for PrP. Mutations and polymorphisms in the PRNP gene can alter PrP amino acid sequence, leading to a change in transmission efficiency depending on the place where it occurs.

Heterogeneity of pathological prion protein accumulation in the brain of moose (Alces alces) from Norway, Sweden and Finland with chronic wasting disease.

Prion diseases are a group of neurodegenerative, transmissible, and fatal disorders that affect several animal species. They are characterized by the conformational conversion of the cellular prion protein (PrP) into the pathological prion protein (PrP). In 2016, chronic wasting disease (CWD) gained great importance at European level due to the first disease detection in a wild reindeer (Rangifer tarandus) in Norway.

Peripheral neuropathy caused by fenugreek () straw intoxication in cattle and experimental reproduction in sheep and goats.

(fenugreek) is a legume widely used as a food supplement in humans and less frequently in ruminants. Toxicity has been described sporadically in ruminants grazing mature fenugreek plants or stubble; however, the pathological features are unclear. This report describes a natural outbreak of intoxication in cattle fed fenugreek straw and the experimental reproduction using 8 sheep and 8 goats.

SARS-CoV-2 Outbreak on a Spanish Mink Farm: Epidemiological, Molecular, and Pathological Studies.

Farmed minks have been reported to be highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may represent a risk to humans. In this study, we describe the first outbreak of SARS-CoV-2 occurred on a mink farm in Spain, between June and July 2020, involving 92,700 animals. The outbreak started shortly after some farm workers became seropositive for SARS-CoV-2.

Classical and Atypical Scrapie in Sheep and Goats. Review on the Etiology, Genetic Factors, Pathogenesis, Diagnosis, and Control Measures of Both Diseases.

Prion diseases, such as scrapie, are neurodegenerative diseases with a fatal outcome, caused by a conformational change of the cellular prion protein (PrP), originating with the pathogenic form (PrP). 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.

Fatal stagger poisoning by consumption of Festuca argentina (Speg.) Parodi in goats from Argentine Patagonia.

The present study describes the spontaneous and experimental poisoning of goats by Festuca argentina in Argentine Patagonia. In April 2017, eight seven-month-old Creole male goats were accidentally introduced into a paddock that contained F. argentina.

Four types of scrapie in goats differentiated from each other and bovine spongiform encephalopathy by biochemical methods.

Scrapie in goats has been known since 1942, the archetype of prion diseases in which only prion protein (PrP) in misfolded state (PrP) acts as infectious agent with fatal consequence. Emergence of bovine spongiform encephalopathy (BSE) with its zoonotic behaviour and detection in goats enhanced fears that its source was located in small ruminants. However, in goats knowledge on prion strain typing is limited.

Low sequence diversity of the prion protein gene (PRNP) in wild deer and goat species from Spain.

The first European cases of chronic wasting disease (CWD) in free-ranging reindeer and wild elk were confirmed in Norway in 2016 highlighting the urgent need to understand transmissible spongiform encephalopathies (TSEs) in the context of European deer species and the many individual populations throughout the European continent. The genetics of the prion protein gene (PRNP) are crucial in determining the relative susceptibility to TSEs. To establish PRNP gene sequence diversity for free-ranging ruminants in the Northeast of Spain, the open reading frame was sequenced in over 350 samples from five species: Iberian red deer (Cervus elaphus hispanicus), roe deer (Capreolus capreolus), fallow deer (Dama dama), Iberian wild goat (Capra pyrenaica hispanica) and Pyrenean chamois (Rupicapra p.

Protein misfolding cyclic amplification corroborates the absence of PrP accumulation in placenta from foetuses with the ARR/ARQ genotype in natural scrapie.

Ovine scrapie is a worldwide spread prion disease that is transmitted horizontally under field conditions. Placenta from scrapie-infected ewes is an important source of infection, since this tissue can accumulate high amounts of PrP depending on the foetal genotype. Therefore, placentas carrying susceptible foetuses can accumulate PrP but there is not PrP accumulation in presence of foetuses with at least one ARR haplotype.

Transmission of sheep-bovine spongiform encephalopathy to pigs.

Experimental transmission of the bovine spongiform encephalopathy (BSE) agent has been successfully reported in pigs inoculated via three simultaneous distinct routes (intracerebral, intraperitoneal and intravenous). Sheep derived BSE (Sh-BSE) is transmitted more efficiently than the original cattle-BSE isolate in a transgenic mouse model expressing porcine prion protein. However, the neuropathology and distribution of Sh-BSE in pigs as natural hosts, and susceptibility to this agent, is unknown.

Influence of polymorphisms in the prion protein gene on the pathogenesis and neuropathological phenotype of sheep scrapie after oral infection.

The prion protein gene (Prnp) plays a crucial role in the susceptibility of sheep to scrapie in terms of attack rate and/or incubation period. However, the influence of Prnp on the pathogenesis of the disease, specifically the involvement of tissues of the lymphoreticular system (LRS), pathways of neuroinvasion and neuropathological phenotypes, remains controversial. This study reports the onset and progression of disease-associated prion protein (PrP(d)) accumulation in the LRS and nervous tissues of sheep of six different Prnp genotypes infected by oral administration of the same mixed scrapie brain homogenate.

Identical pathogenesis and neuropathological phenotype of scrapie in valine, arginine, glutamine/valine, arginine, glutamine sheep infected experimentally by the oral and conjunctival routes.

The pathogenesis of scrapie in sheep after natural or oral exposure to the infectious agent generally involves the early accumulation of disease-associated prion protein (PrP(d)) in the lymphoreticular system (LRS). This phase is followed by neuroinvasion, for which two routes, ascending neural and haematogenous, have been postulated. The present study reports the use of immunohistochemistry to track the tissue progression of PrP(d) deposition in sheep of a single, highly scrapie-susceptible PrP genotype administered by the oral or conjunctival routes.

Prion protein gene variability in Spanish goats. Inference through susceptibility to classical scrapie strains and pathogenic distribution of peripheral PrP(sc.).

Classical scrapie is a neurological disorder of the central nervous system (CNS) characterized by the accumulation of an abnormal, partially protease resistant prion protein (PrP(sc)) in the CNS and in some peripheral tissues in domestic small ruminants. Whereas the pathological changes and genetic susceptibility of ovine scrapie are well known, caprine scrapie has been less well studied. We report here a pathological study of 13 scrapie-affected goats diagnosed in Spain during the last 9 years.

Medulla oblongata transcriptome changes during presymptomatic natural scrapie and their association with prion-related lesions.

Background: The pathogenesis of natural scrapie and other prion diseases is still poorly understood. Determining the variations in the transcriptome in the early phases of the disease might clarify some of the molecular mechanisms of the prion-induced pathology and allow for the development of new biomarkers for diagnosis and therapy. This study is the first to focus on the identification of genes regulated during the preclinical phases of natural scrapie in the ovine medulla oblongata (MO) and the association of these genes with prion deposition, astrocytosis and spongiosis.

Changes in HSP gene and protein expression in natural scrapie with brain damage.

Heat shock proteins (Hsp) perform cytoprotective functions such as apoptosis regulation and inflammatory response control. These proteins can also be secreted to the extracellular medium, acting as inflammatory mediators, and their chaperone activity permits correct folding of proteins and avoids the aggregation of anomalous isoforms. Several studies have proposed the implication of Hsp in prion diseases.

An assessment of the efficiency of PrPsc detection in rectal mucosa and third-eyelid biopsies from animals infected with scrapie.

In classical scrapie, detection of PrPsc on lymphoreticular system is used for the in vivo and post mortem diagnosis of the disease. However, the sensitivity of this methodology is not well characterised because the magnitude and duration of lymphoid tissue involvement can vary considerably. The aim of the present study was to evaluate the efficiency of detecting PrPsc in rectal mucosa and third-eyelid biopsies.

Variability in disease phenotypes within a single PRNP genotype suggests the existence of multiple natural sheep scrapie strains within Europe.

Variability of pathological phenotypes within classical sheep scrapie cases has been reported for some time, but in many instances it has been attributed to differences in the PRNP genotype of the host. To address this issue we have examined by immunohistochemistry (IHC) and Western blotting (WB) for the disease-associated form of the prion protein (PrP(d)), the brains of 23 sheep from five European countries, all of which were of the same ARQ/ARQ genotype. As a result of IHC examinations, sheep were distributed into five groups with different phenotypes and the groups were the same regardless of the scoring method used, 'long' or 'short' PrP(d) profiling.

Detection of PrPSc in lung and mammary gland is favored by the presence of Visna/maedi virus lesions in naturally coinfected sheep.

There are few reports on the pathogenesis of scrapie (Sc) and Visna/maedi virus (VMV) coinfections. The aim of this work was to study in vivo as well as post mortem both diseases in 91 sheep. Diagnosis of Sc and VMV infections allowed the distribution of animals into five groups according to the presence (+) or absence (-) of infection by Sc and VMV: Sc-/VMV-, Sc-/VMV+, Sc+/VMV- and Sc+/VMV+.

Immunohistochemical characterisation of classical scrapie neuropathology in sheep.

Neuroinflammation elicited by PrP(res) (resistant prion protein [PrP]) deposits in the central nervous system (CNS) has been shown to involve cellular and oxidative stress responses in bovine spongiform encephalopathy (BSE) as well as in several murine models of transmissible spongiform encephalopathy (TSE). Additionally, deregulation of water homeostasis has been suggested to be a further component of the spongiform changes observed in TSEs. The aim of the present study was to characterize the pathogenic events occurring in the CNS of sheep with spontaneously arising classical scrapie.