Efficient propagation of variant <scp>C</scp>reutzfeldt‐<scp>J</scp>akob disease prion protein using the cell‐protein misfolding cyclic amplification technique with samples containing plasma and heparin

Oshita, Masatoshi; Yokoyama, Takashi; Takei, Yumiko A.; Takeuchi, Atsuko; Ironside, James W.; Kitamoto, Tetsuyuki; Morita, Masanori

doi:10.1111/trf.13279

Cited by 6 publications

(4 citation statements)

References 58 publications

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“…The significant heterogeneity in the source of PrP C substrates and experimental protocols utilized to date prevents the comparison of current PMCA studies on human prion diseases. Nevertheless, as the most significant finding, most studies revealed a higher seeding activity and amplification efficiency of vCJD and sCJD prions linked to PrP Sc type 2 than in those to PrP Sc type 1 [88,89,90,91,92,95,96,97,98,99,100,101,102,103]. Accordingly, only a few studies have, to date, accomplished an efficient PMCA-amplification of PrP Sc type 1 [88,96,97,101,103].…”

Section: Characterization Of Human Prpsc Types Conversion and Seedmentioning

confidence: 99%

Understanding Prion Strains: Evidence from Studies of the Disease Forms Affecting Humans

Rossi

Baiardi

Parchi

2019

Viruses

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Prion diseases are a unique group of rare neurodegenerative disorders characterized by tissue deposition of heterogeneous aggregates of abnormally folded protease-resistant prion protein (PrPSc), a broad spectrum of disease phenotypes and a variable efficiency of disease propagation in vivo. The dominant clinicopathological phenotypes of human prion disease include Creutzfeldt–Jakob disease, fatal insomnia, variably protease-sensitive prionopathy, and Gerstmann–Sträussler–Scheinker disease. Prion disease propagation into susceptible hosts led to the isolation and characterization of prion strains, initially operatively defined as “isolates” causing diseases with distinctive characteristics, such as the incubation period, the pattern of PrPSc distribution, and the regional severity of neuropathological changes after injection into syngeneic hosts. More recently, the structural basis of prion strains has been linked to amyloid polymorphs (i.e., variant amyloid protein conformations) and the concept extended to all protein amyloids showing polymorphic structures and some evidence of in vivo or in vitro propagation by seeding. Despite the significant advances, however, the link between amyloid structure and disease is not understood in many instances. Here we reviewed the most significant contributions of human prion disease studies to current knowledge of the molecular basis of phenotypic variability and the prion strain phenomenon and underlined the unsolved issues from the human disease perspective.

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Section: Characterization Of Human Prpsc Types Conversion and Seedmentioning

confidence: 99%

Understanding Prion Strains: Evidence from Studies of the Disease Forms Affecting Humans

Rossi

Baiardi

Parchi

2019

Viruses

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“…The improved PMCA assay was shown to have very high sensitivity, as it significantly amplified as little as 10 −18 g of PrP Sc (equivalent to a 10 12 -fold dilution of SHB), as well as high specificity, as it never generated any detectable res PrP in the absence of scrapieinfected brain homogenate inoculum, even after hundreds of PMCA cycles (Saá et al, 2006). When applied to human brain samples (collected either postmortem or by brain biopsy), PrP Sc from sCJD and vCJD patients has been successfully amplified by PMCA (Soto et al, 2005;Jones et al, 2007;Oshita et al, 2016).…”

Section: In Vitro Cell-free Prp Conversion Assaysmentioning

confidence: 99%

“…The PMCA assay has been used to amplify PrP Sc with high sensitivity and specificity from human samples such as blood (Lacroux et al, 2014;Bougard et al, 2016;Concha-Marambio et al, 2016) and urine (Moda et al, 2014). These studies used homogenates from the following biological materials as substrate sources: healthy human brain (Soto et al, 2005), human platelets (Jones et al, 2007), human PrP C -expressing transgenic mouse brain (Jones et al, 2007;Lacroux et al, 2014;Moda et al, 2014;Bougard et al, 2016;Concha-Marambio et al, 2016), and human PrP C -expressing 293F cells (Oshita et al, 2016). Another study has demonstrated that a CDI can be used as a read-out for PMCA to allow the detection of supposed sen PrP Sc species (Jones et al, 2007).…”

Section: (Table 2)mentioning

confidence: 99%

Challenges and Advances in Antemortem Diagnosis of Human Transmissible Spongiform Encephalopathies

Ascari

Rocha

Gonçalves

et al. 2020

Front. Bioeng. Biotechnol.

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Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, arise from the structural conversion of the monomeric, cellular prion protein (PrP C ) into its multimeric scrapie form (PrP Sc ). These pathologies comprise a group of intractable, rapidly evolving neurodegenerative diseases. Currently, a definitive diagnosis of TSE relies on the detection of PrP Sc and/or the identification of pathognomonic histological features in brain tissue samples, which are usually obtained postmortem or, in rare cases, by brain biopsy (antemortem). Over the past two decades, several paraclinical tests for antemortem diagnosis have been developed to preclude the need for brain samples. Some of these alternative methods have been validated and can provide a probable diagnosis when combined with clinical evaluation. Paraclinical tests include in vitro cell-free conversion techniques, such as the real-time quakinginduced conversion (RT-QuIC), as well as immunoassays, electroencephalography (EEG), and brain bioimaging methods, such as magnetic resonance imaging (MRI), whose importance has increased over the years. PrP Sc is the main biomarker in TSEs, and the RT-QuIC assay stands out for its ability to detect PrP Sc in cerebrospinal fluid (CSF), olfactory mucosa, and dermatome skin samples with high sensitivity and specificity. Other biochemical biomarkers are the proteins 14-3-3, tau, neuronspecific enolase (NSE), astroglial protein S100B, α-synuclein, and neurofilament light chain protein (NFL), but they are not specific for TSEs. This paper reviews the techniques employed for definite diagnosis, as well as the clinical and paraclinical methods for possible and probable diagnosis, both those in use currently and those no longer employed. We also discuss current criteria, challenges, and perspectives for TSE diagnosis. An early and accurate diagnosis may allow earlier implementation of strategies to delay or stop disease progression.

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“…Steps for removal and/or inactivation of viruses and prions are always necessary because screening of donors and plasma donations is limited by the number of viruses for which they are screened and the sensitivity of the tests. Furthermore, there is currently no screening test for the detection of prion diseases available [12] as this is still under investigation [17]. Therefore, effective and robust inactivation and/or removal procedures need to be incorporated into the manufacturing processes used in the production of IVIGs.…”

Section: Introductionmentioning

confidence: 99%

Pathogen Safety of a New Intravenous Immune Globulin 10% Liquid

et al. 2017

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BackgroundThe manufacturing process of a new intravenous immune globulin (IVIG) 10% liquid product incorporates two dedicated pathogen safety steps: solvent/detergent (S/D) treatment and nanofiltration (20 nm). Ion-exchange chromatography (IEC) during protein purification also contributes to pathogen safety. The ability of these three process steps to inactivate/remove viruses and prions was evaluated.ObjectivesThe objective of this study was to evaluate the virus and prion safety of the new IVIG 10% liquid.MethodsBovine viral diarrhea virus (BVDV), human immunodeficiency virus type 1 (HIV-1), mouse encephalomyelitis virus (MEV), porcine parvovirus (PPV), and pseudorabies virus (PRV) were used as models for common human viruses. The hamster-adapted scrapie strain 263K (HAS 263K) was used for transmissible spongiform encephalopathies. Virus clearance capacity and robustness of virus reduction were determined for the three steps. Abnormal prion protein (PrPSc) removal and infectivity of the samples was determined.ResultsS/D treatment and nanofiltration inactivated/removed enveloped viruses to below detection limits. IEC supplements viral safety and nanofiltration was highly effective in removing non-enveloped viruses and HAS 263K. Overall virus reduction factors were: ≥9.4 log10 (HIV-1), ≥13.2 log10 (PRV), ≥8.2 log10 (BVDV), ≥11.7 log10 (MEV), ≥11.6 log10 (PPV), and ≥10.4 log10 (HAS 263K).ConclusionTwo dedicated and one supplementing steps in the manufacturing process of the new IVIG 10% liquid provide a high margin of pathogen safety.

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Efficient propagation of variant Creutzfeldt‐Jakob disease prion protein using the cell‐protein misfolding cyclic amplification technique with samples containing plasma and heparin

Abstract: We have established a novel cell-PMCA format in the presence of plasma without any pretreatment, where vCJD prion protein was amplified at comparable levels to that found without plasma. Our data suggest the feasibility of cell-PMCA as a practical blood test for vCJD prions.

Cited by 6 publications

References 58 publications

Understanding Prion Strains: Evidence from Studies of the Disease Forms Affecting Humans

Understanding Prion Strains: Evidence from Studies of the Disease Forms Affecting Humans

Challenges and Advances in Antemortem Diagnosis of Human Transmissible Spongiform Encephalopathies

Pathogen Safety of a New Intravenous Immune Globulin 10% Liquid

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