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.

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 Transmission of the atypical/Nor98 scrapie agent to Suffolk sheep with VRQ/ARQ, ARQ/ARQ, and ARQ/ARR genotypes

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246503
Author(s):  
Eric D. Cassmann ◽  
Najiba Mammadova ◽  
S. Jo Moore ◽  
Sylvie Benestad ◽  
Justin J. Greenlee
Keyword(s):  
Prion Protein ◽  
Transmissible Spongiform Encephalopathy ◽  
Brain Homogenate ◽  
Classical Scrapie ◽  
Spongiform Encephalopathy ◽  
Scrapie Agent ◽  
Suffolk Sheep

Scrapie is a transmissible spongiform encephalopathy that occurs in sheep. Atypical/Nor98 scrapie occurs in sheep that tend to be resistant to classical scrapie and it is thought to occur spontaneously. The purpose of this study was to test the transmission of the Atypical/Nor98 scrapie agent in three genotypes of Suffolk sheep and characterize the distribution of misfolded prion protein (PrPSc). Ten sheep were intracranially inoculated with brain homogenate from a sheep with Atypical/Nor98 scrapie. All sheep with the ARQ/ARQ and ARQ/ARR genotypes developed Atypical/Nor98 scrapie confirmed by immunohistochemistry, and one sheep with the VRQ/ARQ genotype had detectable PrPSc consistent with Atypical/Nor98 scrapie at the experimental endpoint of 8 years. Sheep with mild early accumulations of PrPSc in the cerebellum had concomitant retinal PrPSc. Accordingly, large amounts of retinal PrPSc were identified in clinically affected sheep and sheep with dense accumulations of PrPSc in the cerebellum.

Neuronal Vacuolation in Raccoons (Procyon lotor)

1997 ◽  
Vol 34 (3) ◽  
pp. 250-252 ◽  
Author(s):  
A. N. Hamir ◽  
J. R. Heidel ◽  
R. Picton ◽  
C. E. Rupprecht
Keyword(s):  
United States ◽  
Procyon Lotor ◽  
The United States ◽  
Spongiform Encephalopathy ◽  
Experimental Transmission ◽  
Geographic Locations ◽  
Neuronal Perikaryon ◽  
Naturally Occurring ◽  
Free Ranging ◽  
Neuronal Vacuolation

Microscopic vacuolar changes in neuronal perikaryon are described in two free-ranging raccoons ( Procyon lotor) from different geographic locations in the United States. Both animals were negative for rabies and scrapie-associated antigens. Microscopically, lesions were not seen in the neuropil. Neuronal vacuolations have previously been documented in brains of normal animals and in diseases such as rabies and prion-associated encephalopathies. Although experimental transmission of a spongiform mink encephalopathy has been documented in raccoons, a naturally occurring spongiform encephalopathy has not been described in this species. The presence of neuronal vacuolations in the raccoons is novel and requires further investigation to elucidate the mechanism of this phenomenon.

scholarly journals Reflections on Cerebellar Neuropathology in Classical Scrapie

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 649
Author(s):  
Adolfo Toledano-Díaz ◽  
María Isabel Álvarez ◽  
Jose-Julio Rodríguez ◽  
Juan Jose Badiola ◽  
Marta Monzón ◽  
...  
Keyword(s):  
Prion Protein ◽  
Transmissible Spongiform Encephalopathy ◽  
Classical Scrapie ◽  
Spongiform Encephalopathy ◽  
Insoluble Protein ◽  
Neurotoxic Effects ◽  
Neuronal Types ◽  
Natural Scrapie ◽  
Great Relevance ◽  
Different Origins

In this review, the most important neuropathological changes found in the cerebella of sheep affected by classical natural scrapie are discussed. This disease is the oldest known of a group of unconventional “infections” caused by toxic prions of different origins. Scrapie is currently considered a “transmissible spongiform encephalopathy” (due to its neuropathological characteristics and its transmission), which is the paradigm of prion pathologies as well as many encephalopathies (prion-like) that present aberrant deposits of insoluble protein with neurotoxic effects due to errors in their catabolization (“misfolding protein diseases”). The study of this disease is, therefore, of great relevance. Our work data from the authors’ previous publications as well as other research in the field. The four most important types of neuropathological changes are neuron abnormalities and loss, neurogliosis, tissue vacuolization (spongiosis) and pathological or abnormal prion protein (PrP) deposits/deposition. These findings were analyzed and compared to other neuropathologies. Various aspects related to the presentation and progression of the disease, the involution of different neuronal types, the neuroglial responses and the appearance of abnormal PrP deposits are discussed. The most important points of controversy in scrapie neuropathology are presented.

scholarly journals Atypical prion protein in sheep brain collected during the British scrapie-surveillance programme

2006 ◽  
Vol 87 (2) ◽  
pp. 471-477 ◽  
Author(s):  
S. J. Everest ◽  
L. Thorne ◽  
D. A. Barnicle ◽  
J. C. Edwards ◽  
H. Elliott ◽  
...  
Keyword(s):  
Prion Protein ◽  
Biochemical Analysis ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Spongiform Encephalopathy ◽  
Relative Resistance ◽  
Sheep Population ◽  
Surveillance Programme ◽  
Naturally Occurring ◽  
Sheep Brain

Scrapie of sheep and goats is the most common prion disease (or transmissible spongiform encephalopathy, TSE) of mammals and aggregates of abnormal, proteinase-resistant prion protein (PrPSc) are found in all naturally occurring prion diseases. During active surveillance of British sheep for TSEs, 29 201 sheep brain stem samples were collected from abattoirs and analysed for the presence of PrPSc. Of these samples, 54 were found to be positive by using an ELISA screening test, but 28 of these could not be confirmed initially by immunohistochemistry. These unconfirmed or atypical cases were generally found in PrP genotypes normally associated with relative resistance to clinical scrapie and further biochemical analysis revealed that they contained forms of PrPSc with a relatively protease-sensitive amyloid core, some resembling those of Nor98 scrapie. The presence of these atypical forms of protease-resistant PrP raises concerns that some TSE disorders of PrP metabolism previously may have escaped identification in the British sheep population.

scholarly journals Single nucleotide polymorphisms at 15 codons of the prion protein gene from a scrapie-affected herd of Suffolk sheep in Brazil

2011 ◽  
Vol 31 (10) ◽  
pp. 893-898 ◽  
Author(s):  
Caroline Pinto de Andrade ◽  
Laura Lopes de Almeida ◽  
Luiza Amaral de Castro ◽  
Juliano Souza Leal ◽  
Sergio Ceroni da Silva ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Gene ◽  
Preventive Measures ◽  
Transmissible Spongiform Encephalopathy ◽  
Risk Groups ◽  
Spongiform Encephalopathy ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Rare Polymorphism

Scrapie is a transmissible spongiform encephalopathy of sheeps and goats, associated with the deposition of a isoform of the prion protein (PrPsc). This isoform presents an altered conformation that leads to aggregation in the host's central nervous and lymphoreticular systems. Predisposition to the prion agent infection can be influenced by specific genotypes related to mutations in amino acids of the PrPsc gene. The most characterized mutations occur at codons 136, 154 and 171, with genotypes VRQ being the most susceptible and ARR the most resistant. In this study we have analyzed polymorphisms in 15 different codons of the PrPsc gene in sheeps from a Suffolk herd from Brazil affected by an outbreak of classical scrapie. Amplicons from the PrPsc gene, encompassing the most relevant altered codons in the protein, were sequenced in order to determine each animal's genotype. We have found polymorphisms at 3 of the 15 analyzed codons (136, 143 and 171). The most variable codon was 171, where all described alleles were identified. A rare polymorphism was found at the 143 codon in 4% of the samples analyzed, which has been described as increasing scrapie resistance in otherwise susceptible animals. No other polymorphisms were detected in the remaining 12 analyzed codons, all of them corresponding to the wild-type prion protein. Regarding the risk degree of developing scrapie, most of the animals (96%) had genotypes corresponding to risk groups 1 to 3 (very low to moderate), with only 4% in the higher risks group. Our data is discussed in relation to preventive measures involving genotyping and positive selection to control the disease.

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 Real-Time Quaking-Induced Conversion Detection of PrPSc in Fecal Samples From Chronic Wasting Disease Infected White-Tailed Deer Using Bank Vole Substrate

2021 ◽  
Vol 8 ◽  
Author(s):  
Soyoun Hwang ◽  
Justin J. Greenlee ◽  
Eric M. Nicholson
Keyword(s):  
Real Time ◽  
Chronic Wasting Disease ◽  
Transmissible Spongiform Encephalopathy ◽  
The United States ◽  
Spongiform Encephalopathy ◽  
Post Inoculation ◽  
Sample Type ◽  
Wasting Disease ◽  
Fecal Samples ◽  
Highly Sensitive Detection

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that is fatal to free-range and captive cervids. CWD has been reported in the United States, Canada, South Korea, Norway, Finland, and Sweden, and the case numbers in both wild and farmed cervids are increasing rapidly. Studies indicate that lateral transmission of cervids likely occurs through the shedding of infectious prions in saliva, feces, urine, and blood into the environment. Therefore, the detection of CWD early in the incubation time is advantageous for disease management. In this study, we adapt real-time quacking-induced conversion (RT-QuIC) assays to detect the seeding activity of CWD prions in feces samples from clinical and preclinical white-tailed deer. By optimizing reaction conditions for temperature as well as the salt and salt concentration, prion seeding activity from both clinical and preclinical animals were detected by RT-QuIC. More specifically, all fecal samples collected from 6 to 30 months post inoculation showed seeding activity under the conditions of study. The combination of a highly sensitive detection tool paired with a sample type that may be collected non-invasively allows a useful tool to support CWD surveillance in wild and captive cervids.

scholarly journals Unusual type of scrapie detected in sheep in the United Kingdom

2004 ◽  
Vol 8 (17) ◽  
Author(s):  
Keyword(s):  
United Kingdom ◽  
Brain Tissue ◽  
Transmissible Spongiform Encephalopathy ◽  
Spongiform Encephalopathy ◽  
Tissue Samples ◽  
Sheep And Goats ◽  
The United Kingdom ◽  
Unusual Type

Brain tissue samples from a sheep carcass in the United Kingdom (UK) have undergone tests which have detected a type of scrapie (a transmissible spongiform encephalopathy (TSE) found in sheep and goats) that has not been previously detected

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