Sensitive and specific detection of sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion.

Real-time quaking-induced conversion (RT-QuIC) is an assay in which disease-associated prion protein (PrP) initiates a rapid conformational transition in recombinant PrP (recPrP), resulting in the formation of amyloid that can be monitored in real time using the dye thioflavin T. It therefore has potential advantages over analogous cell-free PrP conversion assays such as protein misfolding cyclic amplification (PMCA). The QuIC assay and the related amyloid seeding assay have been developed largely using rodent-passaged sheep scrapie strains. Given the potential RT-QuIC has for Creutzfeldt-Jakob disease (CJD) research and human prion test development, this study characterized the behaviour of a range of CJD brain specimens with hamster and human recPrP in the RT-QuIC assay. The results showed that RT-QuIC is a rapid, sensitive and specific test for the form of abnormal PrP found in the most commonly occurring forms of sporadic CJD. The assay appeared to be largely independent of species-related sequence differences between human and hamster recPrP and of the methionine/valine polymorphism at codon 129 of the human PrP gene. However, with the same conditions and substrate, the assay was less efficient in detecting the abnormal PrP that characterizes variant CJD brain. Comparison of these QuIC results with those previously obtained using PMCA suggested that these two seemingly similar assays differ in important respects.

[1]  J. Torres,et al.  Molecular Modeling of Prion Transmission to Humans , 2014, Viruses.

[2]  B. Caughey,et al.  Prion Disease Blood Test Using Immunoprecipitation and Improved Quaking-Induced Conversion , 2011, mBio.

[3]  J. Ironside,et al.  Comparison of the level, distribution and form of disease-associated prion protein in variant and sporadic Creutzfeldt-Jakob diseased brain using conformation-dependent immunoassay and Western blot. , 2011, The Journal of general virology.

[4]  Steven J Collins,et al.  Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion , 2011, Nature Medicine.

[5]  Brent Race,et al.  Rapid End-Point Quantitation of Prion Seeding Activity with Sensitivity Comparable to Bioassays , 2010, PLoS pathogens.

[6]  B. Ghetti,et al.  Agent strain variation in human prion disease: insights from a molecular and pathological review of the National Institutes of Health series of experimentally transmitted disease. , 2010, Brain : a journal of neurology.

[7]  Bob Will,et al.  Variant CJD: where has it gone, or has it? , 2010, Practical Neurology.

[8]  M. Bishop,et al.  Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties , 2010, Proceedings of the National Academy of Sciences.

[9]  J. Collinge,et al.  Superoxide Dismutase 1 and tgSOD1G93A Mouse Spinal Cord Seed Fibrils, Suggesting a Propagative Cell Death Mechanism in Amyotrophic Lateral Sclerosis , 2010, PloS one.

[10]  Beat Meier,et al.  Prions , 2010 .

[11]  S. Love,et al.  Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia , 2010, Haemophilia : the official journal of the World Federation of Hemophilia.

[12]  B. Caughey,et al.  Human variant Creutzfeldt-Jakob disease and sheep scrapie PrP(res) detection using seeded conversion of recombinant prion protein. , 2009, Protein engineering, design & selection : PEDS.

[13]  B. Chesebro,et al.  Getting a grip on prions: oligomers, amyloids, and pathological membrane interactions. , 2009, Annual review of biochemistry.

[14]  M. Turner,et al.  An update on the assessment and management of the risk of transmission of variant Creutzfeldt‐Jakob disease by blood and plasma products , 2009, British journal of haematology.

[15]  C. Prowse,et al.  Effects of human PrPSc type and PRNP genotype in an in-vitro conversion assay , 2008, Neuroreport.

[16]  C. Prowse,et al.  Human platelets as a substrate source for the in vitro amplification of the abnormal prion protein (PrPSc) associated with variant Creutzfeldt‐Jakob disease , 2008, Transfusion.

[17]  B. Caughey,et al.  Simplified ultrasensitive prion detection by recombinant PrP conversion with shaking , 2008, Nature Methods.

[18]  M. Turner,et al.  Advances in the development of a screening test for variant Creutzfeldt-Jakob disease. , 2008, Expert opinion on medical diagnostics.

[19]  David W. Colby,et al.  Prion detection by an amyloid seeding assay , 2007, Proceedings of the National Academy of Sciences.

[20]  C. Prowse,et al.  In vitro amplification and detection of variant Creutzfeldt–Jakob disease PrPSc , 2007, The Journal of pathology.

[21]  B. Caughey,et al.  Ultrasensitive detection of scrapie prion protein using seeded conversion of recombinant prion protein , 2007, Nature Methods.

[22]  Suvankar Pal,et al.  Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report , 2006, The Lancet.

[23]  R. Will,et al.  Creutzfeldt–Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiological Review study , 2006, BMJ.

[24]  D. Hilton.  Pathogenesis and prevalence of variant Creutzfeldt–Jakob disease , 2006, The Journal of pathology.

[25]  G. J. Raymond,et al.  The most infectious prion protein particles , 2005, Nature.

[26]  S. Prusiner,et al.  Diagnosis of human prion disease. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Mark Head,et al.  Preclinical variant CJD after blood transfusion in a PRNP codon 129 heterozygous patient , 2004 .

[28]  J Mackenzie,et al.  Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion , 2004, The Lancet.

[29]  Shu G. Chen,et al.  Sporadic and familial CJD: classification and characterisation. , 2003, British medical bulletin.

[30]  V. Uversky,et al.  Probing the mechanism of insulin fibril formation with insulin mutants. , 2001, Biochemistry.

[31]  P Brown,et al.  Classification of sporadic Creutzfeldt‐Jakob disease based on molecular and phenotypic analysis of 300 subjects , 1999, Annals of neurology.

[32]  Stanley B. Prusiner,et al.  Nobel Lecture: Prions , 1998 .

[33]  F. Cohen,et al.  Eight prion strains have PrPSc molecules with different conformations , 1998, Nature Medicine.

[34]  J. Ironside,et al.  The application of in vitro cell-free conversion systems to human prion diseases , 2010, Acta Neuropathologica.

[35]  J Mackenzie,et al.  Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiological Review study. , 2006, Vox sanguinis.

[36]  J. Langeveld,et al.  Immunopathology and Infectious Diseases Detection of Type 1 Prion Protein in Variant Creutzfeldt-Jakob Disease , 2005 .

[37]  C. Sigurdson,et al.  [Prion diseases?]. , 1985, Deutsche medizinische Wochenschrift.

[38]  T. Nikolaus,et al.  Research Letters , 2022 .