classical scrapie
Recently Published Documents


TOTAL DOCUMENTS

105
(FIVE YEARS 17)

H-INDEX

21
(FIVE YEARS 1)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alba Marín-Moreno ◽  
Juan Carlos Espinosa ◽  
Patricia Aguilar-Calvo ◽  
Natalia Fernández-Borges ◽  
José Luis Pitarch ◽  
...  

AbstractE/D163 polymorphism of dog prion protein (PrP) has been recently proposed as the variant responsible for canid prion resistance. To further investigate the protective role of this variant against prion replication, the transgenic mouse model OvPrP-Tg532 expressing sheep/goat PrP carrying the substitution D162 (equivalent to D163 position of dog PrP) was generated and intracranially inoculated with a broad collection of small ruminant prion strains. OvPrP-Tg532 mice showed resistance to classical bovine spongiform encephalopathy (BSE) from sheep and some classical scrapie isolates from sheep and goat but were susceptible to ovine atypical L-BSE and numerous classical scrapie isolates. Strikingly, some of these classical scrapie isolates showed a shift in their prion strain properties. These results suggest that other PrP residues apart from E/D163 variant of dog PrP or factors distinct than PrP may participate in prion resistance of canids and that different factors may be required for D162 sheep PrP to provide effective protection to sheep against ruminant prions.


2021 ◽  
pp. 104063872110176
Author(s):  
Eric D. Cassmann ◽  
Rylie D. Frese ◽  
Justin J. Greenlee

The origin of chronic wasting disease (CWD) in cervids is unclear. One hypothesis suggests that CWD originated from scrapie in sheep. We compared the disease phenotype of sheep-adapted CWD to classical scrapie in sheep. We inoculated sheep intracranially with brain homogenate from first-passage mule deer CWD in sheep (sCWDmd). The attack rate in second-passage sheep was 100% (12 of 12). Sheep had prominent lymphoid accumulations of PrPSc reminiscent of classical scrapie. The pattern and distribution of PrPSc in the brains of sheep with CWDmd was similar to scrapie strain 13-7 but different from scrapie strain x124. The western blot glycoprofiles of sCWDmd were indistinguishable from scrapie strain 13-7; however, independent of sheep genotype, glycoprofiles of sCWDmd were different than x124. When sheep genotypes were evaluated individually, there was considerable overlap in the glycoprofiles that precluded significant discrimination between sheep CWD and scrapie strains. Our data suggest that the phenotype of CWD in sheep is indistinguishable from some strains of scrapie in sheep. Given our results, current detection techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred naturally. It is unknown if sheep are naturally vulnerable to CWD; however, the susceptibility of sheep after intracranial inoculation and lymphoid accumulation indicates that the species barrier is not absolute.


Author(s):  
Pablo Alarcon ◽  
Francisco Marco-Jimenez ◽  
Verity Horigan ◽  
Angel Ortiz-Pelaez ◽  
Brenda Rajanayagam ◽  
...  

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 649
Author(s):  
Adolfo Toledano-Díaz ◽  
María Isabel Álvarez ◽  
Jose-Julio Rodríguez ◽  
Juan Jose Badiola ◽  
Marta Monzón ◽  
...  

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.


2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Alba Marín-Moreno ◽  
Patricia Aguilar-Calvo ◽  
Juan Carlos Espinosa ◽  
María Zamora-Ceballos ◽  
José Luis Pitarch ◽  
...  

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.


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246503
Author(s):  
Eric D. Cassmann ◽  
Najiba Mammadova ◽  
S. Jo Moore ◽  
Sylvie Benestad ◽  
Justin J. Greenlee

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.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243009
Author(s):  
Eric D. Cassmann ◽  
Najiba Mammadova ◽  
Justin J. Greenlee

Scrapie, a prion disease of sheep, is highly resistant to conventional deactivation. Numerous methods to deactivate scrapie have been tested in laboratory animal models, and adequate autoclave treatment can reduce or remove the infectivity of some classical scrapie strains depending on the heating parameters used. In this study, we autoclaved brain homogenate from a sheep with US scrapie strain 13–7 for 30 minutes at 121°C. Genetically susceptible VRQ/ARQ sheep were orally inoculated with 3 grams of the autoclaved brain homogenate. For comparison, a second group of sheep was inoculated with a non-autoclaved brain homogenate. Rectal biopsies were used to assess antemortem scrapie disease progression throughout the study. Five out of ten (5/10) sheep that received autoclaved inoculum ultimately developed scrapie after an experimental endpoint of 72 months. These sheep had a mean incubation period of 26.99 months. Two out of five (2/5) positive sheep had detectable PrPSc in antemortem rectal biopsies, and two (2/5) other sheep had PrPSc in postmortem rectal tissue. A single sheep (1/5) was positive for scrapie in the CNS, small intestine, and retropharyngeal lymph node but had negative rectal tissue. All of the sheep (10/10) that received non-autoclaved inoculum developed scrapie with a mean incubation period of 20.2 months and had positive rectal biopsies at the earliest timepoint (14.7 months post-inoculation). These results demonstrate that sheep are orally susceptible to US derived classical scrapie strain 13–7 after autoclave treatment at 121°C for 30 minutes. Differences in incubation periods and time interval to first positive rectal biopsies indicate a partial reduction in infectivity titers for the autoclaved inoculum group.


2020 ◽  
Vol 7 ◽  
Author(s):  
Timm Konold ◽  
Sonja Libbey ◽  
Brenda Rajanayagam ◽  
Louise Fothergill ◽  
John Spiropoulos ◽  
...  

2020 ◽  
Author(s):  
Eden Yitna Teferedegn ◽  
Yalcin Yaman ◽  
Cemal Un

Abstract Background Classical scrapie susceptibility in sheep has been linked to three polymorphisms at codon 136, 154, and 171 in the prion protein gene (PRNP) whereas atypical scrapie susceptibility is related to polymorphisms at codon 141. Many other variants over the length of the PRNP have been reported. Some of the variants may play crucial roles in fighting against the emergence of a new form of scrapie disease. Scrapie surveillance, scrapie associated genotyping and PRNP characterization studies have been conducted across the globe. However, such in-depth studies have never addressed the African continent’s sheep breeds. Therefore, genotyping native Ethiopian sheep breed’s PRNP gene has socioeconomic and scientific merits. This study aimed to identify PRNP variants in three native Ethiopian sheep breeds and their potential effect on scrapie susceptibility. Results Five novel variants were identified in the PRNP gene of three native Ethiopian sheep breeds. Four non-synonymous heterozygous substitutions i.e. H99Q (CAC-->CAA), H99L (CAC-->CTA), A116E (GCA-->GAA), A116T (GCA-->ACA), and one synonymous N103N (AAC-->AAT) were detected. In addition to the novel variants, polymorphisms at codon 126,127,138,142,146,231, and 237 were also identified. The haplotype ARR was observed in Menz and Afar breeds at frequencies of 0.02 and 0.05 respectively. Neither ARR/ARR nor VRQ/VRQ genotypes were identified in the population under study. Conclusion Two of the novel variants at codon 99 and 103 that are placed closer to the proteinase K cleavage site and the variant at codon 116 in the palindrome region along with variants at codon 127 in glycine repeat domain may influence the conformational flexibility of prion protein. The rarity of ARR haplotype and the abundance of 141L variant demonstrated that the present study population was less resistant to classical scrapie and less predisposed to genotype associated atypical scrapie. This study provides a valuable dataset that can be potentially integrated into selective breeding strategies during interbreeding, crossbreeding and help to take precautionary measures against scrapie.


Sign in / Sign up

Export Citation Format

Share Document