1887

Abstract

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.

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2012-02-01
2019-10-22
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References

  1. Atarashi R. , Moore R. A. , Sim V. L. , Hughson A. G. , Dorward D. W. , Onwubiko H. A. , Priola S. A. , Caughey B. . ( 2007; ). Ultrasensitive detection of scrapie prion protein using seeded conversion of recombinant prion protein. . Nat Methods 4:, 645–650. [CrossRef] [PubMed]
    [Google Scholar]
  2. Atarashi R. , Wilham J. M. , Christensen L. , Hughson A. G. , Moore R. A. , Johnson L. M. , Onwubiko H. A. , Priola S. A. , Caughey B. . ( 2008; ). Simplified ultrasensitive prion detection by recombinant PrP conversion with shaking. . Nat Methods 5:, 211–212. [CrossRef] [PubMed]
    [Google Scholar]
  3. Atarashi R. , Satoh K. , Sano K. , Fuse T. , Yamaguchi N. , Ishibashi D. , Matsubara T. , Nakagaki T. , Yamanaka H. et al. ( 2011; ). Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion. . Nat Med 17:, 175–178. [CrossRef] [PubMed]
    [Google Scholar]
  4. Bishop M. T. , Will R. G. , Manson J. C. . ( 2010; ). Defining sporadic Creutzfeldt–Jakob disease strains and their transmission properties. . Proc Natl Acad Sci U S A 107:, 12005–12010. [CrossRef] [PubMed]
    [Google Scholar]
  5. Brown P. , Brandel J. P. , Preece M. , Sato T. . ( 2006; ). Iatrogenic Creutzfeldt–Jakob disease: the waning of an era. . Neurology 67:, 389–393. [CrossRef] [PubMed]
    [Google Scholar]
  6. Caughey B. , Baron G. S. , Chesebro B. , Jeffrey M. . ( 2009; ). Getting a grip on prions: oligomers, amyloids, and pathological membrane interactions. . Annu Rev Biochem 78:, 177–204. [CrossRef] [PubMed]
    [Google Scholar]
  7. Chia R. , Tattum M. H. , Jones S. , Collinge J. , Fisher E. M. , Jackson G. S. . ( 2010; ). Superoxide dismutase 1 and tgSOD1 mouse spinal cord seed fibrils, suggesting a propagative cell death mechanism in amyotrophic lateral sclerosis. . PLoS ONE 5:, e10627. [CrossRef] [PubMed]
    [Google Scholar]
  8. Choi Y. P. , Gröner A. , Ironside J. W. , Head M. W. . ( 2011; ). 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. . J Gen Virol 92:, 727–732. [CrossRef] [PubMed]
    [Google Scholar]
  9. Colby D. W. , Zhang Q. , Wang S. , Groth D. , Legname G. , Riesner D. , Prusiner S. B. . ( 2007; ). Prion detection by an amyloid seeding assay. . Proc Natl Acad Sci U S A 104:, 20914–20919. [CrossRef] [PubMed]
    [Google Scholar]
  10. Gambetti P. , Kong Q. , Zou W. , Parchi P. , Chen S. G. . ( 2003; ). Sporadic and familial CJD: classification and characterisation. . Br Med Bull 66:, 213–239. [CrossRef] [PubMed]
    [Google Scholar]
  11. Hewitt P. E. , Llewelyn C. A. , Mackenzie J. , Will R. G. . ( 2006; ). Creutzfeldt–Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiological Review study. . Vox Sang 91:, 221–230. [CrossRef] [PubMed]
    [Google Scholar]
  12. Hilton D. A. . ( 2006; ). Pathogenesis and prevalence of variant Creutzfeldt–Jakob disease. . J Pathol 208:, 134–141. [CrossRef] [PubMed]
    [Google Scholar]
  13. Ironside J. W. , Ghetti B. , Head M. W. , Piccardo P. , Will R. G. . ( 2008; ). Prion diseases. . In Greenfield's Neuropathology, Vol. 2. 8th edn , pp. 1197–1273. Edited by Love S. , Louis D. N. , Ellison D. W. . . London:: Hodder and Arnold;.[CrossRef]
    [Google Scholar]
  14. Jones M. , Peden A. H. , Prowse C. V. , Gröner A. , Manson J. C. , Turner M. L. , Ironside J. W. , MacGregor I. R. , Head M. W. . ( 2007; ). In vitro amplification and detection of variant Creutzfeldt–Jakob disease PrPSc . . J Pathol 213:, 21–26. [CrossRef] [PubMed]
    [Google Scholar]
  15. Jones M. , Peden A. H. , Wight D. , Prowse C. , Macgregor I. , Manson J. , Turner M. , Ironside J. W. , Head M. W. . ( 2008; ). Effects of human PrPSc type and PRNP genotype in an in-vitro conversion assay. . Neuroreport 19:, 1783–1786. [CrossRef] [PubMed]
    [Google Scholar]
  16. Jones M. , Peden A. H. , Yull H. , Wight D. , Bishop M. T. , Prowse C. V. , Turner M. L. , Ironside J. W. , MacGregor I. R. , Head M. W. . ( 2009a; ). Human platelets as a substrate source for the in vitro amplification of the abnormal prion protein (PrP) associated with variant Creutzfeldt–Jakob disease. . Transfusion 49:, 376–384. [CrossRef] [PubMed]
    [Google Scholar]
  17. Jones M. , Wight D. , Barron R. , Jeffrey M. , Manson J. , Prowse C. , Ironside J. W. , Head M. W. . ( 2009b; ). Molecular model of prion transmission to humans. . Emerg Infect Dis 15:, 2013–2016. [CrossRef] [PubMed]
    [Google Scholar]
  18. Jones M. , Peden A. H. , Head M. W. , Ironside J. W. . ( 2011; ). The application of in vitro cell-free conversion systems to human prion diseases. . Acta Neuropathol 121:, 135–143. [CrossRef] [PubMed]
    [Google Scholar]
  19. Llewelyn C. A. , Hewitt P. E. , Knight R. S. , Amar K. , Cousens S. , Mackenzie J. , Will R. G. . ( 2004; ). Possible transmission of variant Creutzfeldt–Jakob disease by blood transfusion. . Lancet 363:, 417–421. [CrossRef] [PubMed]
    [Google Scholar]
  20. Nielsen L. , Frokjaer S. , Brange J. , Uversky V. N. , Fink A. L. . ( 2001; ). Probing the mechanism of insulin fibril formation with insulin mutants. . Biochemistry 40:, 8397–8409. [CrossRef] [PubMed]
    [Google Scholar]
  21. Orrú C. D. , Wilham J. M. , Hughson A. G. , Raymond L. D. , McNally K. L. , Bossers A. , Ligios C. , Caughey B. . ( 2009; ). Human variant Creutzfeldt–Jakob disease and sheep scrapie PrPres detection using seeded conversion of recombinant prion protein. . Protein Eng Des Sel 22:, 515–521. [CrossRef] [PubMed]
    [Google Scholar]
  22. Orrú C. D. , Wilham J. M. , Raymond L. D. , Kuhn F. , Schroeder B. , Raeber A. J. , Caughey B. . ( 2011; ). Prion disease blood test using immunoprecipitation and improved quaking-induced conversion. . MBio 2:, e00078-11. [CrossRef] [PubMed]
    [Google Scholar]
  23. Parchi P. , Giese A. , Capellari S. , Brown P. , Schulz-Schaeffer W. , Windl O. , Zerr I. , Budka H. , Kopp N. et al. ( 1999; ). Classification of sporadic Creutzfeldt–Jakob disease based on molecular and phenotypic analysis of 300 subjects. . Ann Neurol 46:, 224–233. [CrossRef] [PubMed]
    [Google Scholar]
  24. Parchi P. , Cescatti M. , Notari S. , Schulz-Schaeffer W. J. , Capellari S. , Giese A. , Zou W. Q. , Kretzschmar H. , Ghetti B. , Brown P. . ( 2010; ). 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. . Brain 133:, 3030–3042. [CrossRef] [PubMed]
    [Google Scholar]
  25. Peden A. H. , Head M. W. , Ritchie D. L. , Bell J. E. , Ironside J. W. . ( 2004; ). Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. . Lancet 364:, 527–529. [CrossRef] [PubMed]
    [Google Scholar]
  26. Peden A. H. , Head M. W. , Jones M. , MacGregor I. R. , Turner M. L. , Ironside J. W. . ( 2008; ). Advances in the development of a screening test for variant Creutzfeldt–Jakob disease. . Expert Opin Med Diagn 2:, 207–219. [CrossRef]
    [Google Scholar]
  27. Peden A. , McCardle L. , Head M. W. , Love S. , Ward H. J. , Cousens S. N. , Keeling D. M. , Millar C. M. , Hill F. G. , Ironside J. W. . ( 2010; ). Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia. . Haemophilia 16:, 296–304. [CrossRef] [PubMed]
    [Google Scholar]
  28. Prusiner S. B. . ( 1998; ). Prions. . Proc Natl Acad Sci U S A 95:, 13363–13383. [CrossRef] [PubMed]
    [Google Scholar]
  29. Safar J. , Wille H. , Itri V. , Groth D. , Serban H. , Torchia M. , Cohen F. E. , Prusiner S. B. . ( 1998; ). Eight prion strains have PrPSc molecules with different conformations. . Nat Med 4:, 1157–1165. [CrossRef] [PubMed]
    [Google Scholar]
  30. Safar J. G. , Geschwind M. D. , Deering C. , Didorenko S. , Sattavat M. , Sanchez H. , Serban A. , Vey M. , Baron H. et al. ( 2005; ). Diagnosis of human prion disease. . Proc Natl Acad Sci U S A 102:, 3501–3506. [CrossRef] [PubMed]
    [Google Scholar]
  31. Silveira J. R. , Raymond G. J. , Hughson A. G. , Race R. E. , Sim V. L. , Hayes S. F. , Caughey B. . ( 2005; ). The most infectious prion protein particles. . Nature 437:, 257–261. [CrossRef] [PubMed]
    [Google Scholar]
  32. Turner M. L. , Ludlam C. A. . ( 2009; ). An update on the assessment and management of the risk of transmission of variant Creutzfeldt–Jakob disease by blood and plasma products. . Br J Haematol 144:, 14–23. [CrossRef] [PubMed]
    [Google Scholar]
  33. Wilham J. M. , Orrú C. D. , Bessen R. A. , Atarashi R. , Sano K. , Race B. , Meade-White K. D. , Taubner L. M. , Timmes A. , Caughey B. . ( 2010; ). Rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays. . PLoS Pathog 6:, e1001217. [CrossRef] [PubMed]
    [Google Scholar]
  34. Will B. . ( 2010; ). Variant CJD: where has it gone, or has it?. Pract Neurol 10:, 250–251. [CrossRef] [PubMed]
    [Google Scholar]
  35. Wroe S. J. , Pal S. , Siddique D. , Hyare H. , Macfarlane R. , Joiner S. , Linehan J. M. , Brandner S. , Wadsworth J. D. et al. ( 2006; ). Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt–Jakob disease associated with blood transfusion: a case report. . Lancet 368:, 2061–2067. [CrossRef] [PubMed]
    [Google Scholar]
  36. Yull H. M. , Ritchie D. L. , Langeveld J. P. , van Zijderveld F. G. , Bruce M. E. , Ironside J. W. , Head M. W. . ( 2006; ). Detection of type 1 prion protein in variant Creutzfeldt–Jakob disease. . Am J Pathol 168:, 151–157. [CrossRef] [PubMed]
    [Google Scholar]
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