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 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.

Measuring prions causing bovine spongiform encephalopathy or chronic wasting disease by immunoassays and transgenic mice

2002 ◽  
Vol 20 (11) ◽  
pp. 1147-1150 ◽  
Author(s):  
Jiri G. Safar ◽  
Michael Scott ◽  
Jeff Monaghan ◽  
Camille Deering ◽  
Svetlana Didorenko ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Bovine Spongiform Encephalopathy ◽  
Chronic Wasting Disease ◽  
Spongiform Encephalopathy ◽  
Wasting Disease

Bovine Spongiform Encephalopathy and Scrapie: Potential Human Hazards

1989 ◽  
Vol 18 (4) ◽  
pp. 165-168 ◽  
Author(s):  
W. F. Blakemore
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Infectious Agent ◽  
Infected Sheep ◽  
Spongiform Encephalopathy

Bovine spongiform encephalopathy (BSE), a recently recognized disease of cattle, resulted from the incorporation of scrapie-infected sheep tissue into cattle food. BSE and scrapie are members of a group of transmissible diseases caused by an unconventional infectious agent, some of which affect man. As these diseases can cross species barriers this new bovine disease may represent a potential disease hazard to man.

scholarly journals Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein

2012 ◽  
Vol 93 (7) ◽  
pp. 1624-1629 ◽  
Author(s):  
Rona Wilson ◽  
Chris Plinston ◽  
Nora Hunter ◽  
Cristina Casalone ◽  
Cristiano Corona ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Chronic Wasting Disease ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Wild Type ◽  
Wasting Disease ◽  
Spongiform Encephalopathies ◽  
Jakob Disease ◽  
Human Prion Protein

The association between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt–Jakob disease (vCJD) has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health and raises the possibility that other ruminant TSEs may be transmissible to humans. In recent years, several novel TSEs in sheep, cattle and deer have been described and the risk posed to humans by these agents is currently unknown. In this study, we inoculated two forms of atypical BSE (BASE and H-type BSE), a chronic wasting disease (CWD) isolate and seven isolates of atypical scrapie into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP). Upon challenge with these ruminant TSEs, gene-targeted Tg mice expressing human PrP did not show any signs of disease pathology. These data strongly suggest the presence of a substantial transmission barrier between these recently identified ruminant TSEs and humans.

scholarly journals Susceptibility of Cattle to First-passage Intracerebral Inoculation with Chronic Wasting Disease Agent from White-tailed Deer

2007 ◽  
Vol 44 (4) ◽  
pp. 487-493 ◽  
Author(s):  
A. N. Hamir ◽  
J. M. Miller ◽  
R. A. Kunkle ◽  
S. M. Hall ◽  
J. A. Richt
Keyword(s):  
Chronic Wasting Disease ◽  
Prion Diseases ◽  
Clinical Signs ◽  
Diagnostic Techniques ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Spongiform Encephalopathies ◽  
Disease Agent ◽  
Sheep Scrapie

Fourteen, 3-month-old calves were intracerebrally inoculated with the agent of chronic wasting disease (CWD) from white-tailed deer (CWDwtd) to compare the clinical signs and neuropathologic findings with those of certain other transmissible spongiform encephalopathies (TSE, prion diseases) that have been shown to be experimentally transmissible to cattle (sheep scrapie, CWD of mule deer [CWDmd], bovine spongiform encephalopathy [BSE], and transmissible mink encephalopathy). Two uninoculated calves served as controls. Within 26 months postinoculation (MPI), 12 inoculated calves had lost considerable weight and eventually became recumbent. Of the 12 inoculated calves, 11 (92%) developed clinical signs. Although spongiform encephalopathy (SE) was not observed, abnormal prion protein (PrPd) was detected by immunohistochemistry (IHC) and Western blot (WB) in central nervous system tissues. The absence of SE with presence of PrPd has also been observed when other TSE agents (scrapie and CWDmd) were similarly inoculated into cattle. The IHC and WB findings suggest that the diagnostic techniques currently used to confirm BSE would detect CWDwtd in cattle, should it occur naturally. Also, the absence of SE and a distinctive IHC pattern of CWDwtd and CWDmd in cattle suggests that it should be possible to distinguish these conditions from other TSEs that have been experimentally transmitted to cattle.

scholarly journals Exposure Risk of Chronic Wasting Disease in Humans

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1454
Author(s):  
Satish K. Nemani ◽  
Jennifer L. Myskiw ◽  
Lise Lamoureux ◽  
Stephanie A. Booth ◽  
Valerie L. Sim
Keyword(s):  
Chronic Wasting Disease ◽  
Prion Diseases ◽  
Causal Link ◽  
In Vivo Studies ◽  
Spongiform Encephalopathy ◽  
Strain Typing ◽  
Species Barrier ◽  
Wasting Disease

The majority of human prion diseases are sporadic, but acquired disease can occur, as seen with variant Creutzfeldt–Jakob disease (vCJD) following consumption of bovine spongiform encephalopathy (BSE). With increasing rates of cervid chronic wasting disease (CWD), there is concern that a new form of human prion disease may arise. Currently, there is no evidence of transmission of CWD to humans, suggesting the presence of a strong species barrier; however, in vitro and in vivo studies on the zoonotic potential of CWD have yielded mixed results. The emergence of different CWD strains is also concerning, as different strains can have different abilities to cross species barriers. Given that venison consumption is common in areas where CWD rates are on the rise, increased rates of human exposure are inevitable. If CWD was to infect humans, it is unclear how it would present clinically; in vCJD, it was strain-typing of vCJD prions that proved the causal link to BSE. Therefore, the best way to screen for CWD in humans is to have thorough strain-typing of harvested cervids and human CJD cases so that we will be in a position to detect atypical strains or strain shifts within the human CJD population.

scholarly journals Detection and Discrimination of Classical and Atypical L-Type Bovine Spongiform Encephalopathy by Real-Time Quaking-Induced Conversion

2015 ◽  
Vol 53 (4) ◽  
pp. 1115-1120 ◽  
Author(s):  
Christina D. Orrú ◽  
Alessandra Favole ◽  
Cristiano Corona ◽  
Maria Mazza ◽  
Matteo Manca ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Real Time ◽  
Brain Tissue ◽  
Prion Protein ◽  
Rapid Detection ◽  
Prion Diseases ◽  
Spongiform Encephalopathy ◽  
Diagnostic Strategy ◽  
The Real ◽  
Recombinant Prion Protein

Statutory surveillance of bovine spongiform encephalopathy (BSE) indicates that cattle are susceptible to both classical BSE (C-BSE) and atypical forms of BSE. Atypical forms of BSE appear to be sporadic and thus may never be eradicated. A major challenge for prion surveillance is the lack of sufficiently practical and sensitive tests for routine BSE detection and strain discrimination. The real-time quaking-induced conversion (RT-QuIC) test, which is based on prion-seeded fibrillization of recombinant prion protein (rPrPSen), is known to be highly specific and sensitive for the detection of multiple human and animal prion diseases but not BSE. Here, we tested brain tissue from cattle affected by C-BSE and atypical L-type bovine spongiform encephalopathy (L-type BSE or L-BSE) with the RT-QuIC assay and found that both BSE forms can be detected and distinguished using particular rPrPSensubstrates. Specifically, L-BSE was detected using multiple rPrPSensubstrates, while C-BSE was much more selective. This substrate-based approach suggests a diagnostic strategy for specific, sensitive, and rapid detection and discrimination of at least some BSE forms.

Zombie deer and the species barrier. Should humans worry about it?

2020 ◽  
Keyword(s):  
Chronic Disease ◽  
Bovine Spongiform Encephalopathy ◽  
Chronic Wasting Disease ◽  
Spongiform Encephalopathy ◽  
Species Barrier ◽  
Wasting Disease ◽  
Prion Infection ◽  
The Moment

This commentary reports of a deer chronic disease (chronic wasting disease - CWD), which might be transmitted to humans. It is due to a prion infection, similar to the bovine spongiform encephalopathy (BSE). At the moment, it is not known if the disease may be transmitted to humans. That is why all of us should be aware of the disease, and more careful while consuming deer meat.

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 Prion Protein Devoid of the Octapeptide Repeat Region Delays Bovine Spongiform Encephalopathy Pathogenesis in Mice

2017 ◽  
Vol 92 (1) ◽  
Author(s):  
Hideyuki Hara ◽  
Hironori Miyata ◽  
Nandita Rani Das ◽  
Junji Chida ◽  
Tatenobu Yoshimochi ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Prion Diseases ◽  
Spongiform Encephalopathy ◽  
Wild Type ◽  
Jakob Disease ◽  
Function Relationship ◽  
Different Strains ◽  
Conformational Conversion

ABSTRACTConformational conversion of the cellular isoform of prion protein, PrPC, into the abnormally folded, amyloidogenic isoform, PrPSc, is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals. We previously reported that the octapeptide repeat (OR) region could be dispensable for converting PrPCinto PrPScafter infection with RML prions. We demonstrated that mice transgenically expressing mouse PrP with deletion of the OR region on the PrP knockout background, designated Tg(PrPΔOR)/Prnp0/0mice, did not show reduced susceptibility to RML scrapie prions, with abundant accumulation of PrPScΔOR in their brains. We show here that Tg(PrPΔOR)/Prnp0/0mice were highly resistant to BSE prions, developing the disease with markedly elongated incubation times after infection with BSE prions. The conversion of PrPΔOR into PrPScΔOR was markedly delayed in their brains. These results suggest that the OR region may have a crucial role in the conversion of PrPCinto PrPScafter infection with BSE prions. However, Tg(PrPΔOR)/Prnp0/0mice remained susceptible to RML and 22L scrapie prions, developing the disease without elongated incubation times after infection with RML and 22L prions. PrPScΔOR accumulated only slightly less in the brains of RML- or 22L-infected Tg(PrPΔOR)/Prnp0/0mice than PrPScin control wild-type mice. Taken together, these results indicate that the OR region of PrPCcould play a differential role in the pathogenesis of BSE prions and RML or 22L scrapie prions.IMPORTANCEStructure-function relationship studies of PrPCconformational conversion into PrPScare worthwhile to understand the mechanism of the conversion of PrPCinto PrPSc. We show here that, by inoculating Tg(PrPΔOR)/Prnp0/0mice with the three different strains of RML, 22L, and BSE prions, the OR region could play a differential role in the conversion of PrPCinto PrPScafter infection with RML or 22L scrapie prions and BSE prions. PrPΔOR was efficiently converted into PrPScΔOR after infection with RML and 22L prions. However, the conversion of PrPΔOR into PrPScΔOR was markedly delayed after infection with BSE prions. Further investigation into the role of the OR region in the conversion of PrPCinto PrPScafter infection with BSE prions might be helpful for understanding the pathogenesis of BSE prions.

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