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

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Jan P. M. Langeveld ◽  
Laura Pirisinu ◽  
Jorg G. Jacobs ◽  
Maria Mazza ◽  
Isabelle Lantier ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Small Ruminants ◽  
Infectious Agent ◽  
Spongiform Encephalopathy ◽  
Prion Strain ◽  
Amino Acid Region ◽  
Proteolytic Resistance ◽  
Fatal Consequence

AbstractScrapie in goats has been known since 1942, the archetype of prion diseases in which only prion protein (PrP) in misfolded state (PrPSc) 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. A European-wide study is presented concerning the biochemical phenotypes of the protease resistant fraction of PrPSc (PrPres) in over thirty brain isolates from transmissible spongiform encephalopathy (TSE) affected goats collected in seven countries. Three different scrapie forms were found: classical scrapie (CS), Nor98/atypical scrapie and one case of CH1641 scrapie. In addition, CS was found in two variants—CS-1 and CS-2 (mainly Italy)—which differed in proteolytic resistance of the PrPresN-terminus. Suitable PrPres markers for discriminating CH1641 from BSE (C-type) appeared to be glycoprofile pattern, presence of two triplets instead of one, and structural (in)stability of its core amino acid region. None of the samples exhibited BSE like features. BSE and these four scrapie types, of which CS-2 is new, can be recognized in goats with combinations of a set of nine biochemical parameters.

scholarly journals Increased susceptibility of transgenic mice expressing human PrP to experimental sheep bovine spongiform encephalopathy is not due to increased agent titre in sheep brain tissue

2014 ◽  
Vol 95 (8) ◽  
pp. 1855-1859 ◽  
Author(s):  
Chris Plinston ◽  
Patricia Hart ◽  
Nora Hunter ◽  
Jean C. Manson ◽  
Rona M. Barron
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Brain Tissue ◽  
Transmissible Spongiform Encephalopathy ◽  
Small Ruminants ◽  
Infectious Agent ◽  
Spongiform Encephalopathy ◽  
Jakob Disease ◽  
Human Prion Protein ◽  
Sheep Brain ◽  
Increased Susceptibility

Bovine spongiform encephalopathy (BSE) in cattle and variant Creutzfeldt–Jakob disease in humans have previously been shown to be caused by the same strain of transmissible spongiform encephalopathy agent. It is hypothesized that the agent spread to humans following consumption of food products prepared from infected cattle. Despite evidence supporting zoonotic transmission, mouse models expressing human prion protein (HuTg) have consistently shown poor transmission rates when inoculated with cattle BSE. Higher rates of transmission have however been observed when these mice are exposed to BSE that has been experimentally transmitted through sheep or goats, indicating that humans may potentially be more susceptible to BSE from small ruminants. Here we demonstrate that increased transmissibility of small ruminant BSE to HuTg mice was not due to replication of higher levels of infectivity in sheep brain tissue, and is instead due to other specific changes in the infectious agent.

scholarly journals Lymphotoxin-α- and Lymphotoxin-β-Deficient Mice Differ in Susceptibility to Scrapie: Evidence against Dendritic Cell Involvement in Neuroinvasion

2002 ◽  
Vol 76 (9) ◽  
pp. 4357-4363 ◽  
Author(s):  
Michael B. A. Oldstone ◽  
Richard Race ◽  
Diane Thomas ◽  
Hanna Lewicki ◽  
Dirk Homann ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Oral Intake ◽  
Infectious Agent ◽  
Lymphoid Cells ◽  
Current Evidence ◽  
Spongiform Encephalopathy ◽  
Lymphoid Tissues ◽  
Mesenteric Lymph Nodes

ABSTRACT Transmissible spongiform encephalopathy or prion diseases are fatal neurodegenerative disorders of humans and animals often initiated by oral intake of an infectious agent. Current evidence suggests that infection occurs initially in the lymphoid tissues and subsequently in the central nervous system (CNS). The identity of infected lymphoid cells remains controversial, but recent studies point to the involvement of both follicular dendritic cells (FDC) and CD11c+ lymphoid dendritic cells. FDC generation and maintenance in germinal centers is dependent on lymphotoxin alpha (LT-α) and LT-β signaling components. We report here that by the oral route, LT-α −/− mice developed scrapie while LT-β −/− mice did not. Furthermore, LT-α −/− mice had a higher incidence and shorter incubation period for developing disease following inoculation than did LT-β −/− mice. Transplantation of lymphoid tissues from LT-β −/− mice, which have cervical and mesenteric lymph nodes, into LT-α −/− mice, which do not, did not alter the incidence of CNS scrapie. In other studies, a virus that is tropic for and alters functions of CD11c+ cells did not alter the kinetics of neuroinvasion of scrapie. Our results suggest that neither FDC nor CD11c+ cells are essential for neuroinvasion after high doses of RML scrapie. Further, it is possible that an as yet unidentified cell found more abundantly in LT-α −/− than in LT-β −/− mice may assist in the amplification of scrapie infection in the periphery and favor susceptibility to CNS disease following peripheral routes of infection.

scholarly journals Transmissible spongiform encephalopathy strain, PrP genotype and brain region all affect the degree of glycosylation of PrPSc

2005 ◽  
Vol 86 (1) ◽  
pp. 241-246 ◽  
Author(s):  
Robert A. Somerville ◽  
Scott Hamilton ◽  
Karen Fernie
Keyword(s):  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Infectious Agent ◽  
Host Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Major Influence ◽  
Spongiform Encephalopathy ◽  
Phenotypic Properties ◽  
Spongiform Encephalopathies ◽  
Diagnostic Potential

Transmissible spongiform encephalopathies (TSEs), sometimes known as prion diseases, are caused by an infectious agent whose molecular properties have not been determined. Traditionally, different strains of TSE diseases are characterized by a series of phenotypic properties after passage in experimental animals. More recently it has been recognized that diversity in the degree to which an abnormal form of the host protein PrP, denoted PrPSc, is glycosylated and the migration of aglycosyl forms of PrPSc on immunoblots may have some differential diagnostic potential. It has been recognized that these factors are affected by the strain of TSE agent but also by other factors, e.g. location within the brain. This study shows in some cases, but not others, that host PrP genotype has a major influence on the degree of PrPSc glycosylation and migration on gels and provides further evidence of the effect of brain location. Accordingly both the degree of glycosylation and the apparent molecular mass of PrPSc may be of some value for differential diagnosis between TSE strains, but only when host effects are taken into account. Furthermore, the data inform the debate about how these differences arise, and favour hypotheses proposing that TSE agents affect glycosylation of PrP during its biosynthesis.

scholarly journals Identification of Misfolded Proteins in Body Fluids for the Diagnosis of Prion Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Francesca Properzi ◽  
Maurizio Pocchiari
Keyword(s):  
Prion Protein ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Clinical Signs ◽  
Meat Products ◽  
Silent Period ◽  
Infectious Agent ◽  
Body Fluids ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy

Transmissible spongiform encephalopathy (TSE) or prion diseases are fatal rare neurodegenerative disorders affecting man and animals and caused by a transmissible infectious agent. TSE diseases are characterized by spongiform brain lesions with neuronal loss and the abnormal deposition in the CNS, and to less extent in other tissues, of an insoluble and protease resistant form of the cellular prion protein (PrPC), namedPrPTSE. In man, TSE diseases affect usually people over 60 years of age with no evident disease-associated risk factors. In some cases, however, TSE diseases are unequivocally linked to infectious episodes related to the use of prion-contaminated medicines, medical devices, or meat products as in the variant Creutzfeldt-Jakob disease (CJD). Clinical signs occur months or years after infection, and during this silent periodPrPTSE, the only reliable marker of infection, is not easily measurable in blood or other accessible tissues or body fluids causing public health concerns. To overcome the limit ofPrPTSEdetection, several highly sensitive assays have been developed, but attempts to apply these techniques to blood of infected hosts have been unsuccessful or not yet validated. An update on the latest advances for the detection of misfolded prion protein in body fluids is provided.

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

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 691
Author(s):  
Cristina Acín ◽  
Rosa Bolea ◽  
Marta Monzón ◽  
Eva Monleón ◽  
Bernardino Moreno ◽  
...  
Keyword(s):  
Prion Protein ◽  
Genetic Factors ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Fatal Outcome ◽  
Small Ruminants ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy ◽  
Atypical Scrapie ◽  
Sheep And Goats

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

scholarly journals Detection of RNA in the Plasma of Patients with Sporadic Creutzfeldt–Jakob Disease, Gerstmann–Straüssler Syndrome and Other Non-Transmissible Spongiform Encephalopathy Brain Disorders

2010 ◽  
Vol 3 ◽  
pp. MBI.S4043
Author(s):  
Kazuo Tsukui ◽  
Yasushi Iwasaki ◽  
Masamitsu Nagaoka ◽  
Kenji Tadokoro
Keyword(s):  
Prion Protein ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Infectious Agent ◽  
Brain Homogenate ◽  
Proteinase K ◽  
Spongiform Encephalopathy ◽  
Brain Disorders ◽  
Rna Molecules ◽  
Jakob Disease

The infectious agent of transmissible spongiform encephalopathy (TSE) was assumed to be the aggregate of abnormal prion protein isoform (PrPsc). We observed that lowering the pH of 3% SDS-inoculated plasma or brain homogenate after PK digestion to 4.5 (acidic SDS condition) enabled to precipitate proteinase K-resistant prion protein (PrPres) in plasma as well as PrPres in the brain with synthetic poly-A RNA as affinity aggregate. Therefore, we determined if RNA molecules could be used for discriminating TSE patients from healthy individuals. We also examined the plasma of patients with classical Creutzfeldt–Jakob disease (CJD) and other brain disorders who were not diagnosed with TSE. The results indicated that RNA approximately 1.5–2.0 kb in length was commonly observed in the plasma of patients with brain disorders but was not detected in the plasma of healthy volunteers. Enhanced expression of RNA and its protection from endogenous nucleases might occur in the former group of patients. Moreover, we speculate that the non-transmissible neuronal disorders overlap with prion diseases.

scholarly journals Diagnosis of Transmissible Spongiform Encephalopathies in Animals: A Review

2005 ◽  
Vol 17 (6) ◽  
pp. 509-527 ◽  
Author(s):  
Dolores Gavier-Widén ◽  
Michael J. Stack ◽  
Thierry Baron ◽  
Aru Balachandran ◽  
Marion Simmons
Keyword(s):  
Prion Diseases ◽  
Small Ruminants ◽  
Immunohistochemical Analysis ◽  
Considerable Effect ◽  
Proteinase K ◽  
Screening Tests ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Spongiform Encephalopathies ◽  
Prion Strain

Transmissible spongiform encephalopathies (TSEs) in animals include, among others, bovine spongiform encephalopathy (BSE), scrapie, chronic wasting disease, and atypical forms of prion diseases. Diagnosis of TSEs is based on identification of characteristic lesions or on detection of the abnormal prion proteins in tissues, often by use of their partial proteinase K resistance property. Correctly sampling of target tissues is of utmost importance as this has a considerable effect on test sensitivity. Most of the rapid or screening tests are based on ELISA or Western immunoblot (WB) analysis, and many are officially approved. Confirmatory testing is normally performed by use of histologic examination, immunohistochemical analysis, certain WB protocols, or detection of prion fibrils by use of electron microscopy (scrapie-associated fibril). The discriminatory methods for diagnostic use are mostly based on WB technology and provide initial identification of the prion strain, particularly for differentiation of BSE from scrapie in small ruminants. Definitive prion strain characterization is performed by use of bioassays, usually in mice. A burgeoning number of transgenic mice have been developed for TSE studies. Development of new tests with higher sensitivity and of more reliable diagnostic applications for live animals tested for food safety reasons is a rapidly developing field. Ultimately, the choice of a test for TSE diagnosis depends on the rationale for the testing.

scholarly journals Nature of cross-seeding barriers of amyloidogenesis.

2012 ◽  
Vol 59 (2) ◽  
Author(s):  
Dariusz Stępkowski ◽  
Juliusz Bieniaś
Keyword(s):  
Experimental Data ◽  
Bovine Spongiform Encephalopathy ◽  
Theoretical Approach ◽  
Prion Diseases ◽  
Infectious Agent ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Molecular Nature ◽  
Dissimilarity Function ◽  
Occurrence Of Species

The epidemics of bovine spongiform encephalopathy (BSE) several decades ago and present epidemics of chronic wasting disease (CWD) among cervids posed a threat of cross-species infections to humans or other animals. Therefore, the question as to the molecular nature of the species barriers to transmissibility of prion diseases is very important. We approached this problem theoretically, first developing a model of template-monomer interaction based on logical and topological grounds and on experimental data about cross-seeding of PrP 23-144 protein orthologs. Further, we propose that the strength of the cross-seeding barriers is proportional to dissimilarity of key amyloidogenic regions of the proteins. This dissimilarity can be measured by dissimilarity function we propose. Scaled on experimental data, this function predicts if cross-seeding can occur between different variants of PrP23-144. The resemblance of PrP23-144 cross-seeding barriers to the barriers of cross-species transmissibility of prion diseases is discussed. We suggest that a similar theoretical approach could be applied to predicting the occurrence of species barriers of prion diseases at least in part corresponding to the process of multiplication of infectious agent.

scholarly journals PrP P102L and Nearby Lysine Mutations Promote Spontaneous In Vitro Formation of Transmissible Prions

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Allison Kraus ◽  
Gregory J. Raymond ◽  
Brent Race ◽  
Katrina J. Campbell ◽  
Andrew G. Hughson ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Clinical Signs ◽  
Protein Aggregates ◽  
Structural Features ◽  
Spongiform Encephalopathy ◽  
Specific Sequence

ABSTRACT Accumulation of fibrillar protein aggregates is a hallmark of many diseases. While numerous proteins form fibrils by prion-like seeded polymerization in vitro, only some are transmissible and pathogenic in vivo. To probe the structural features that confer transmissibility to prion protein (PrP) fibrils, we have analyzed synthetic PrP amyloids with or without the human prion disease-associated P102L mutation. The formation of infectious prions from PrP molecules in vitro has required cofactors and/or unphysiological denaturing conditions. Here, we demonstrate that, under physiologically compatible conditions without cofactors, the P102L mutation in recombinant hamster PrP promoted prion formation when seeded by minute amounts of scrapie prions in vitro. Surprisingly, combination of the P102L mutation with charge-neutralizing substitutions of four nearby lysines promoted spontaneous prion formation. When inoculated into hamsters, both of these types of synthetic prions initiated substantial accumulation of prion seeding activity and protease-resistant PrP without transmissible spongiform encephalopathy (TSE) clinical signs or notable glial activation. Our evidence suggests that PrP's centrally located proline and lysine residues act as conformational switches in the in vitro formation of transmissible PrP amyloids. IMPORTANCE Many diseases involve the damaging accumulation of specific misfolded proteins in thread-like aggregates. These threads (fibrils) are capable of growing on the ends by seeding the refolding and incorporation of the normal form of the given protein. In many cases such aggregates can be infectious and propagate like prions when transmitted from one individual host to another. Some transmitted aggregates can cause fatal disease, as with human iatrogenic prion diseases, while other aggregates appear to be relatively innocuous. The factors that distinguish infectious and pathogenic protein aggregates from more innocuous ones are poorly understood. Here we have compared the combined effects of prion seeding and mutations of prion protein (PrP) on the structure and transmission properties of synthetic PrP aggregates. Our results highlight the influence of specific sequence features in the normally unstructured region of PrP that influence the infectious and neuropathogenic properties of PrP-derived aggregates.

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