scholarly journals Microglial Cell Line Established from Prion Protein-Overexpressing Mice Is Susceptible to Various Murine Prion Strains

2006 ◽  
Vol 81 (3) ◽  
pp. 1524-1527 ◽  
Author(s):  
Yoshifumi Iwamaru ◽  
Takato Takenouchi ◽  
Kazumasa Ogihara ◽  
Megumi Hoshino ◽  
Masuhiro Takata ◽  
...  
Keyword(s):  
Cell Line ◽  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Cell Lines ◽  
Microglial Cell ◽  
Prion Diseases ◽  
Spongiform Encephalopathy ◽  
Prion Strains ◽  
Microglial Cell Line ◽  
Lines Of Evidence

ABSTRACT Several lines of evidence suggest that microglia have important roles in the pathogenesis of prion diseases. Here, we establish a novel microglial cell line (MG20) from neonatal tga20 mice that overexpress murine prion protein. After exposure to Chandler scrapie, we observed the replication and accumulation of disease-associated forms of the prion protein in MG20 cells up to the 15th passage. Furthermore, MG20 cells were susceptible to ME7, Obihiro scrapie, and bovine spongiform encephalopathy agents. Thus, MG20 cell lines persistently infected with various murine prion strains provide a useful model for the study of the pathogenesis of prion diseases.

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.

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.

scholarly journals A field on fire: The biochemistry of mad cows

2005 ◽  
Vol 27 (4) ◽  
pp. 6-8
Author(s):  
David R. Brown
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Prion Disease ◽  
Prion Diseases ◽  
Human Diseases ◽  
Spongiform Encephalopathy ◽  
Related Disease ◽  
Jakob Disease ◽  
Sporadic Cjd

Prion diseases are neurodegenerative diseases1 that have been linked together because they may potentially have the same cause. These include the diseases scrapie of sheep and BSE (bovine spongiform encephalopathy) of cattle, and also several human diseases that include sporadic CJD (Creutzfeldt-Jakob) disease and a variety of inherited forms. The inherited forms of prion diseases are linked to mutations within the gene for the prion protein. Around 85% of all human cases of prion disease are sporadic CJD, which is a disease affecting people of around 60 years of age. The cause of this disease remains unknown. Unfortunately, the name of this disease causes some confusion, as it is similar to vCJD (variant CJD), a related disease of much younger people.

scholarly journals Characterization of two distinct prion strains derived from bovine spongiform encephalopathy transmissions to inbred mice

2004 ◽  
Vol 85 (8) ◽  
pp. 2471-2478 ◽  
Author(s):  
Sarah E. Lloyd ◽  
Jacqueline M. Linehan ◽  
Melanie Desbruslais ◽  
Susan Joiner ◽  
Jennifer Buckell ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Incubation Time ◽  
Inbred Mice ◽  
Biochemical Properties ◽  
Distinct Pattern ◽  
Spongiform Encephalopathy ◽  
Prion Strain ◽  
Disease Phenotypes ◽  
Prion Strains

Distinct prion strains can be distinguished by differences in incubation period, neuropathology and biochemical properties of disease-associated prion protein (PrPSc) in inoculated mice. Reliable comparisons of mouse prion strain properties can only be achieved after passage in genetically identical mice, as host prion protein sequence and genetic background are known to modulate prion disease phenotypes. While multiple prion strains have been identified in sheep scrapie and Creutzfeldt–Jakob disease, bovine spongiform encephalopathy (BSE) is thought to be caused by a single prion strain. Primary passage of BSE prions to different lines of inbred mice resulted in the propagation of two distinct PrPSc types, suggesting that two prion strains may have been isolated. To investigate this further, these isolates were subpassaged in a single line of inbred mice (SJL) and it was confirmed that two distinct prion strains had been identified. MRC1 was characterized by a short incubation time (110±3 days), a mono-glycosylated-dominant PrPSc type and a generalized diffuse pattern of PrP-immunoreactive deposits, while MRC2 displayed a much longer incubation time (155±1 days), a di-glycosylated-dominant PrPSc type and a distinct pattern of PrP-immunoreactive deposits and neuronal loss. These data indicate a crucial involvement of the host genome in modulating prion strain selection and propagation in mice. It is possible that multiple disease phenotypes may also be possible in BSE prion infection in humans and other animals.

scholarly journals Differential Accumulation of Misfolded Prion Strains in Natural Hosts of Prion Diseases

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2453
Author(s):  
Zoe J. Lambert ◽  
Justin J. Greenlee ◽  
Eric D. Cassmann ◽  
M. Heather West Greenlee
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Prion Diseases ◽  
Brain Regions ◽  
Cellular Prion Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Prion Strains ◽  
Natural Hosts ◽  
Different Strains

Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of neurodegenerative protein misfolding diseases that invariably cause death. TSEs occur when the endogenous cellular prion protein (PrPC) misfolds to form the pathological prion protein (PrPSc), which templates further conversion of PrPC to PrPSc, accumulates, and initiates a cascade of pathologic processes in cells and tissues. Different strains of prion disease within a species are thought to arise from the differential misfolding of the prion protein and have different clinical phenotypes. Different strains of prion disease may also result in differential accumulation of PrPSc in brain regions and tissues of natural hosts. Here, we review differential accumulation that occurs in the retinal ganglion cells, cerebellar cortex and white matter, and plexuses of the enteric nervous system in cattle with bovine spongiform encephalopathy, sheep and goats with scrapie, cervids with chronic wasting disease, and humans with prion diseases. By characterizing TSEs in their natural host, we can better understand the pathogenesis of different prion strains. This information is valuable in the pursuit of evaluating and discovering potential biomarkers and therapeutics for prion diseases.

scholarly journals Porcine Prion Protein as a Paradigm of Limited Susceptibility to Prion Strain Propagation

2020 ◽  
Author(s):  
Juan Carlos Espinosa ◽  
Alba Marín-Moreno ◽  
Patricia Aguilar-Calvo ◽  
Sylvie L Benestad ◽  
Olivier Andreoletti ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Conformational Flexibility ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy ◽  
Prion Strain ◽  
Experimental Transmission ◽  
Prion Strains ◽  
Jakob Disease

Abstract Although experimental transmission of bovine spongiform encephalopathy (BSE) to pigs and transgenic mice expressing pig cellular prion protein (PrPC) (porcine PrP [PoPrP]–Tg001) has been described, no natural cases of prion diseases in pig were reported. This study analyzed pig-PrPC susceptibility to different prion strains using PoPrP-Tg001 mice either as animal bioassay or as substrate for protein misfolding cyclic amplification (PMCA). A panel of isolates representatives of different prion strains was selected, including classic and atypical/Nor98 scrapie, atypical-BSE, rodent scrapie, human Creutzfeldt-Jakob-disease and classic BSE from different species. Bioassay proved that PoPrP-Tg001-mice were susceptible only to the classic BSE agent, and PMCA results indicate that only classic BSE can convert pig-PrPC into scrapie-type PrP (PrPSc), independently of the species origin. Therefore, conformational flexibility constraints associated with pig-PrP would limit the number of permissible PrPSc conformations compatible with pig-PrPC, thus suggesting that pig-PrPC may constitute a paradigm of low conformational flexibility that could confer high resistance to the diversity of prion strains.

scholarly journals Detection and characterization of proteinase K-sensitive disease-related prion protein with thermolysin

2008 ◽  
Vol 416 (2) ◽  
pp. 297-305 ◽  
Author(s):  
Sabrina Cronier ◽  
Nathalie Gros ◽  
M. Howard Tattum ◽  
Graham S. Jackson ◽  
Anthony R. Clarke ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Diseases ◽  
Rocky Mountain ◽  
Proteinase K ◽  
Spongiform Encephalopathy ◽  
Prion Strains ◽  
Human Counterpart ◽  
Jakob Disease ◽  
The Brain

Disease-related PrPSc [pathogenic PrP (prion protein)] is classically distinguished from its normal cellular precursor, PrPC(cellular PrP) by its detergent insolubility and partial resistance to proteolysis. Although molecular diagnosis of prion disease has historically relied upon detection of protease-resistant fragments of PrPSc using PK (proteinase K), it is now apparent that a substantial fraction of disease-related PrP is destroyed by this protease. Recently, thermolysin has been identified as a complementary tool to PK, permitting isolation of PrPSc in its full-length form. In the present study, we show that thermolysin can degrade PrPC while preserving both PK-sensitive and PK-resistant isoforms of disease-related PrP in both rodent and human prion strains. For mouse RML (Rocky Mountain Laboratory) prions, the majority of PK-sensitive disease-related PrP isoforms do not appear to contribute significantly to infectivity. In vCJD (variant Creutzfeldt–Jakob disease), the human counterpart of BSE (bovine spongiform encephalopathy), up to 90% of total PrP present in the brain resists degradation with thermolysin, whereas only ∼15% of this material resists digestion by PK. Detection of PK-sensitive isoforms of disease-related PrP using thermolysin should be useful for improving diagnostic sensitivity in human prion diseases.

scholarly journals Detection of Atypical H-Type Bovine Spongiform Encephalopathy and Discrimination of Bovine Prion Strains by Real-Time Quaking-Induced Conversion

2016 ◽  
Vol 54 (3) ◽  
pp. 676-686 ◽  
Author(s):  
Kentaro Masujin ◽  
Christina D. Orrú ◽  
Kohtaro Miyazawa ◽  
Bradley R. Groveman ◽  
Lynne D. Raymond ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Real Time ◽  
Prion Diseases ◽  
Proteinase K ◽  
Spongiform Encephalopathy ◽  
Reaction Products ◽  
Protein Substrates ◽  
Prion Strains ◽  
Recombinant Prion Protein ◽  
Classical Bovine Spongiform Encephalopathy

Prion diseases of cattle include the classical bovine spongiform encephalopathy (C-BSE) and the atypical H-type BSE (H-BSE) and L-type BSE (L-BSE) strains. Although the C- and L-BSE strains can be detected and discriminated by ultrasensitive real-time quaking-induced conversion (RT-QuIC) assays, no such test has yet been described for the detection of H-BSE or the discrimination of each of the major bovine prion strains. Here, we demonstrate an RT-QuIC assay for H-BSE that can detect as little as 10−9dilutions of brain tissue and neat cerebrospinal fluid samples from clinically affected cattle. Moreover, comparisons of the reactivities with different recombinant prion protein substrates and/or immunoblot band profiles of proteinase K-treated RT-QuIC reaction products indicated that H-, L-, and C-BSE have distinctive prion seeding activities and can be discriminated by RT-QuIC on this basis.

Sign in / Sign up

Export Citation Format

Share Document