scholarly journals Classical scrapie in small ruminants is caused by at least four different prion strains

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Alba Marín-Moreno ◽  
Patricia Aguilar-Calvo ◽  
Juan Carlos Espinosa ◽  
María Zamora-Ceballos ◽  
José Luis Pitarch ◽  
...  
Keyword(s):  
Transmissible Spongiform Encephalopathy ◽  
Small Ruminants ◽  
Classical Scrapie ◽  
Spongiform Encephalopathy ◽  
Rodent Models ◽  
Species Barrier ◽  
Single Strain ◽  
Prion Strains ◽  
Scrapie Strains

AbstractThe 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) PrPC. 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.

scholarly journals Review: Update on Classical and Atypical Scrapie in Sheep and Goats

2018 ◽  
Vol 56 (1) ◽  
pp. 6-16 ◽  
Author(s):  
Justin J. Greenlee
Keyword(s):  
Prion Protein ◽  
Environmental Contamination ◽  
Protein Misfolding ◽  
Transmissible Spongiform Encephalopathy ◽  
Classical Scrapie ◽  
Spongiform Encephalopathy ◽  
Atypical Scrapie ◽  
Sheep And Goats ◽  
Scrapie Agent ◽  
Scrapie Strains

Scrapie is a naturally occurring transmissible spongiform encephalopathy (TSE) or prion disease of sheep and goats. Scrapie is a protein misfolding disease where the normal prion protein (PrPC) misfolds into a pathogenic form (PrPSc) that is highly resistant to enzymatic breakdown within the cell and accumulates, eventually leading to neurodegeneration. The amino acid sequence of the prion protein and tissue distribution of PrPSc within affected hosts have a major role in determining susceptibility to and potential environmental contamination with the scrapie agent. Many countries have genotype-based eradication programs that emphasize using rams that express arginine at codon 171 in the prion protein, which is associated with resistance to the classical scrapie agent. In classical scrapie, accumulation of PrPSc within lymphoid and other tissues facilitates environmental contamination and spread of the disease within flocks. A major distinction can be made between classical scrapie strains that are readily spread within populations of susceptible sheep and goats and atypical (Nor-98) scrapie that has unique molecular and phenotype characteristics and is thought to occur spontaneously in older sheep or goats. This review provides an overview of classical and atypical scrapie with consideration of potential transmission of classical scrapie to other mammalian hosts.

scholarly journals Species-Independent Inhibition of Abnormal Prion Protein (PrP) Formation by a Peptide Containing a Conserved PrP Sequence

1999 ◽  
Vol 73 (8) ◽  
pp. 6245-6250 ◽  
Author(s):  
Joëlle Chabry ◽  
Suzette A. Priola ◽  
Kathy Wehrly ◽  
Jane Nishio ◽  
James Hope ◽  
...  
Keyword(s):  
Prion Protein ◽  
Transmissible Spongiform Encephalopathy ◽  
Neuroblastoma Cell ◽  
Spongiform Encephalopathy ◽  
Inhibitory Effects ◽  
Mouse Neuroblastoma Cell ◽  
Mouse Neuroblastoma ◽  
Scrapie Strain ◽  
Species Specific ◽  
Scrapie Strains

ABSTRACT Conversion of the normal protease-sensitive prion protein (PrP) to its abnormal protease-resistant isoform (PrP-res) is a major feature of the pathogenesis associated with transmissible spongiform encephalopathy (TSE) diseases. In previous experiments, PrP conversion was inhibited by a peptide composed of hamster PrP residues 109 to 141, suggesting that this region of the PrP molecule plays a crucial role in the conversion process. In this study, we used PrP-res derived from animals infected with two different mouse scrapie strains and one hamster scrapie strain to investigate the species specificity of these conversion reactions. Conversion of PrP was found to be completely species specific; however, despite having three amino acid differences, peptides corresponding to the hamster and mouse PrP sequences from residues 109 to 141 inhibited both the mouse and hamster PrP conversion systems equally. Furthermore, a peptide corresponding to hamster PrP residues 119 to 136, which was identical in both mouse and hamster PrP, was able to inhibit PrP-res formation in both the mouse and hamster cell-free systems as well as in scrapie-infected mouse neuroblastoma cell cultures. Because the PrP region from 119 to 136 is very conserved in most species, this peptide may have inhibitory effects on PrP conversion in a wide variety of TSE diseases.

scholarly journals Characterization of an unusual transmissible spongiform encephalopathy in goat by transmission in knock-in transgenic mice

2013 ◽  
Vol 94 (8) ◽  
pp. 1922-1932 ◽  
Author(s):  
Rona Wilson ◽  
Declan King ◽  
Nora Hunter ◽  
Wilfred Goldmann ◽  
Rona M. Barron
Keyword(s):  
Unusual Case ◽  
Neurodegenerative Disorder ◽  
Transmissible Spongiform Encephalopathy ◽  
Small Ruminants ◽  
Dairy Goat ◽  
Spongiform Encephalopathy ◽  
Variant Form ◽  
Sheep And Goats ◽  
The Uk ◽  
Mouse Lines

Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disorder of cattle, and its transmission to humans through contaminated food is thought to be the cause of the variant form of Creutzfeldt–Jakob disease. BSE is believed to have spread from the recycling in cattle of ruminant tissue in meat and bone meal (MBM). However, during this time, sheep and goats were also exposed to BSE-contaminated MBM. Both sheep and goats are experimentally susceptible to BSE, and while there have been no reported natural BSE cases in sheep, two goat BSE field cases have been documented. While cases of BSE are rare in small ruminants, the existence of scrapie in both sheep and goats is well established. In the UK, during 2006–2007, a serious outbreak of clinical scrapie was detected in a large dairy goat herd. Subsequently, 200 goats were selected for post-mortem examination, one of which showed biochemical and immunohistochemical features of the disease-associated prion protein (PrPTSE) which differed from all other infected goats. In the present study, we investigated this unusual case by performing transmission bioassays into a panel of mouse lines. Following characterization, we found that strain properties such as the ability to transmit to different mouse lines, lesion profile pattern, degree of PrP deposition in the brain and biochemical features of this unusual goat case were neither consistent with goat BSE nor with a goat scrapie herdmate control. However, our results suggest that this unusual case has BSE-like properties and highlights the need for continued surveillance.

scholarly journals Transmissible spongiform encephalopathy in goats: is PrP rapid test sensitivity affected by genotype?

2020 ◽  
Vol 32 (1) ◽  
pp. 87-93 ◽  
Author(s):  
Marion M. Simmons ◽  
Leigh Thorne ◽  
Angel Ortiz-Pelaez ◽  
John Spiropoulos ◽  
Soteria Georgiadou ◽  
...  
Keyword(s):  
Transmissible Spongiform Encephalopathy ◽  
Small Ruminants ◽  
Rapid Test ◽  
Prnp Gene ◽  
Spongiform Encephalopathy ◽  
Sheep Population ◽  
Test Sensitivity ◽  
Goat Population ◽  
Clinical Stages ◽  
Rapid Tests

Transmissible spongiform encephalopathy (TSE) surveillance in goats relies on tests initially approved for cattle, subsequently assessed for sheep, and approval extrapolated for use in “small ruminants.” The current EU-approved immunodetection tests employ antibodies against various epitopes of the prion protein PrPSc, which is encoded by the host PRNP gene. The caprine PRNP gene is polymorphic, mostly at codons different from the ovine PRNP. The EU goat population is much more heterogeneous than the sheep population, with more PRNP-related polymorphisms, and with marked breed-related differences. The ability of the current tests to detect disease-specific PrPSc generated against these different genetic backgrounds is currently assumed, rather than proven. We examined whether common polymorphisms within the goat PRNP gene might have any adverse effect on the relative performance of EU-approved rapid tests. The sample panel comprised goats from the UK, Cyprus, France, and Italy, with either experimental or naturally acquired scrapie at both the preclinical and/or unknown and clinical stages of disease. Test sensitivity was significantly lower and more variable when compared using samples from animals that were preclinical or of unknown status. However, all of the rapid tests included in our study were able to correctly identify all samples from animals in the clinical stages of disease, apart from samples from animals polymorphic for serine or aspartic acid at codon 146, in which the performance of the Bio-Rad tests was profoundly affected. Our data show that some polymorphisms may adversely affect one test and not another, as well as underline the dangers of extrapolating from other species.

scholarly journals Blood Chimerism Confounds Genetic Relative Susceptibility Testing for Classical Scrapie in Sheep

2009 ◽  
Vol 21 (3) ◽  
pp. 295-305 ◽  
Author(s):  
David A. Schneider ◽  
Ahmed Tibary ◽  
Terje Raudsepp ◽  
Pranab J. Das ◽  
Katherine I. O'Rourke
Keyword(s):  
Susceptibility Testing ◽  
Transmissible Spongiform Encephalopathy ◽  
The United States ◽  
Classical Scrapie ◽  
Spongiform Encephalopathy ◽  
Nucleotide Polymorphisms ◽  
Tissue Samples ◽  
Relative Susceptibility ◽  
Prnp Genotype ◽  
Naturally Occurring

Classical scrapie disease is a transmissible spongiform encephalopathy of sheep that is enzootic in the United States. Susceptibility of sheep to classical scrapie is linked to single nucleotide polymorphisms in the prion protein gene ( PRNP), forming the basis for genetic testing strategies used by national efforts to eradicate scrapie. Such efforts are occasionally hampered by inconclusive results stemming from the detection of “complex” genotypes. Naturally occurring cases of ovine chimerism are thought to account for some of these instances. In the current report, 4 naturally occurring ovine chimeras are documented through cytogenetic and molecular analyses. All 4 of these sheep had chimeric cells circulating in their blood. Blood and alternate tissue samples of ear punch and hair bulbs from one of these chimeras was submitted in batch with similar samples from control sheep for routine scrapie genetic relative susceptibility testing. A complex PRNP genotype was detected in the blood of the chimeric female but not in the alternate tissue samples or in the control sheep samples. The results demonstrate that naturally occurring blood chimerism can confound current testing efforts. The potential impacts of undetected chimeras on current scrapie eradication efforts are discussed.

Comparison of Brain PrPd Distribution in Ovine BSE and Scrapie

2011 ◽  
Vol 48 (6) ◽  
pp. 1101-1108 ◽  
Author(s):  
S. Lezmi ◽  
T. Seuberlich ◽  
A. Oevermann ◽  
T. Baron ◽  
A. Bencsik
Keyword(s):  
Frontal Cortex ◽  
Prion Diseases ◽  
Piriform Cortex ◽  
Small Ruminants ◽  
Infected Sheep ◽  
Spongiform Encephalopathy ◽  
Genotype Distribution ◽  
Prion Strains ◽  
Incubation Periods ◽  
The Brain

Scrapie and bovine spongiform encephalopathy (BSE) are both prion diseases affecting ruminants, and these diseases do not share the same public health concerns. Surveillance of the BSE agent in small ruminants has been a great challenge, and the recent identification of diverse prion diseases in ruminants has led to the development of new methods for strain typing. In our study, using immunohistochemistry (IHC), we assessed the distribution of PrPd in the brains of 2 experimentally BSE-infected sheep with the ARQ/ARQ genotype. Distribution of PrPd in the brain, from the spinal cord to the frontal cortex, was remarkably similar in the 2 sheep despite different inoculation routes and incubation periods. Comparatively, overall PrPd brain distribution, evaluated by IHC, in 19 scrapie cases with the ARQ/ARQ, ARQ/VRQ, and VRQ/VRQ genotypes, in some cases showed similarities to the experimentally BSE-infected sheep. There was no exclusive neuroanatomical site with a characteristic and specific PrPd type of accumulation induced by the BSE agent. However, a detailed analysis of the topography, types, and intensity of PrPd deposits in the frontal cortex, striatum, piriform cortex, hippocampus, mesencephalon, and cerebellum allowed the BSE-affected sheep group to be distinguished from the 19 scrapie cases analyzed in our study. These results strengthen and emphasize the potential interest of PrPd brain mapping to help in identifying prion strains in small ruminants.

scholarly journals Molecular Profiling of Ovine Prion Diseases by Using Thermolysin-Resistant PrPSc and Endogenous C2 PrP Fragments

2007 ◽  
Vol 81 (19) ◽  
pp. 10532-10539 ◽  
Author(s):  
Jonathan P. Owen ◽  
Helen C. Rees ◽  
Ben C. Maddison ◽  
Linda A. Terry ◽  
Leigh Thorne ◽  
...  
Keyword(s):  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Spongiform Encephalopathy ◽  
Western Blots ◽  
Sheep Population ◽  
Natural Scrapie ◽  
Caudal Medulla ◽  
Scrapie Strains

ABSTRACT Disease-associated PrP fragments produced upon in vitro or in vivo proteolysis can provide significant insight into the causal strain of prion disease. Here we describe a novel molecular strain typing assay that used thermolysin digestion of caudal medulla samples to produce PrPres signatures on Western blots that readily distinguished experimental sheep bovine spongiform encephalopathy (BSE) from classical scrapie. Furthermore, the accumulation of such PrPres species within the cerebellum also appeared to be dependent upon the transmissible spongiform encephalopathy (TSE) strain, allowing discrimination between two experimental strains of scrapie and grouping of natural scrapie isolates into two profiles. The occurrence of endogenously produced PrP fragments, namely, glycosylated and unglycosylated C2, within different central nervous system (CNS) regions is also described; this is the first detailed description of such scrapie-associated fragments within a natural host. The advent of C2 fragments within defined CNS regions, compared between BSE and scrapie cases and also between two experimental scrapie strains, appeared to be largely dependent upon the TSE strain. The combined analyses of C2 fragments and thermolysin-resistant PrP species within caudal medulla, cerebellum, and spinal cord samples allowed natural scrapie isolates to be separated into four distinct molecular profiles: most isolates produced C2 and PrPres in all CNS regions, a second group lacked detectable cerebellar C2 fragments, one isolate lacked both cerebellar PrPres and C2, and a further isolate lacked detectable C2 within all three CNS regions and also lacked cerebellar PrPres. This CNS region-specific deposition of disease-associated PrP species may reflect the natural heterogeneity of scrapie strains in the sheep population in the United Kingdom.

scholarly journals Relevance of oral experimental challenge with classical scrapie in sheep

2010 ◽  
Vol 91 (8) ◽  
pp. 2139-2144 ◽  
Author(s):  
Guillaume Tabouret ◽  
Caroline Lacroux ◽  
Séverine Lugan ◽  
Pierrette Costes ◽  
Fabien Corbière ◽  
...  
Keyword(s):  
Incubation Period ◽  
Prion Protein ◽  
Transmissible Spongiform Encephalopathy ◽  
Classical Scrapie ◽  
Spongiform Encephalopathy ◽  
Lymphoid Tissues ◽  
Relevant Model ◽  
Experimental Conditions ◽  
Oral Inoculation ◽  
Experimental Challenge

Oral inoculation is currently considered as the best approach to mimic natural TSE contamination in ruminants. In this study, we compared the timing of abnormal prion protein (PrPSc) dissemination and accumulation in the organism of susceptible sheep either orally inoculated or naturally infected with classical scrapie. Both animal groups shared a similar PrPSc dissemination scheme and accumulation dynamics in lymphoid tissues. However, orally challenged animals displayed an earlier neuro-invasion and a dramatically shorter incubation period than naturally exposed sheep. No differences were observed between the groups with regards to the neuro-invasion route. These results unambiguously indicate that oral inoculation can have an impact on both the earliness of neuro-invasion and the incubation period. They also support the statement that oral inoculation is a relevant model for investigating transmissible spongiform encephalopathy pathogenesis. Nevertheless, data obtained under such experimental conditions should be used with some caution.

scholarly journals Characterization of goat prions demonstrates geographical variation of scrapie strains in Europe and reveals the composite nature of prion strains

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Romolo Nonno ◽  
Alba Marin-Moreno ◽  
Juan Carlos Espinosa ◽  
Christine Fast ◽  
Lucien Van Keulen ◽  
...  
Keyword(s):  
Small Ruminants ◽  
Direct Interaction ◽  
Biological Properties ◽  
Spongiform Encephalopathy ◽  
Strain Diversity ◽  
Wide Range ◽  
Strain Components ◽  
Composite Strain ◽  
Composite Nature ◽  
Scrapie Strains

AbstractBovine Spongiform Encephalopathy (BSE) is the only animal prion which has been recognized as a zoonotic agent so far. The identification of BSE in two goats raised the need to reliably identify BSE in small ruminants. However, our understanding of scrapie strain diversity in small ruminants remains ill-defined, thus limiting the accuracy of BSE surveillance and spreading fear that BSE might lurk unrecognized in goats. We investigated prion strain diversity in a large panel of European goats by a novel experimental approach that, instead of assessing the neuropathological profile after serial transmissions in a single animal model, was based on the direct interaction of prion isolates with several recipient rodent models expressing small ruminants or heterologous prion proteins. The findings show that the biological properties of scrapie isolates display different patterns of geographical distribution in Europe and suggest that goat BSE could be reliably discriminated from a wide range of biologically and geographically diverse goat prion isolates. Finally, most field prion isolates showed composite strain features, with discrete strain components or sub-strains being present in different proportions in individual goats or tissues. This has important implications for understanding the nature and evolution of scrapie strains and their transmissibility to other species, including humans.

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