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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.033365-0
2012-02-01
2022-01-24
Loading full text...

Full text loading...

/deliver/fulltext/jgv/93/2/438.html?itemId=/content/journal/jgv/10.1099/vir.0.033365-0&mimeType=html&fmt=ahah

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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][PubMed]
    [Google Scholar]
  12. Hilton D. A. 2006; Pathogenesis and prevalence of variant Creutzfeldt–Jakob disease. J Pathol 208:134–141 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article]
    [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 [View Article][PubMed]
    [Google Scholar]
  28. Prusiner S. B. 1998; Prions. Proc Natl Acad Sci U S A 95:13363–13383 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][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 [View Article][PubMed]
    [Google Scholar]
  34. Will B. 2010; Variant CJD: where has it gone, or has it?. Pract Neurol 10:250–251 [View Article][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 [View Article][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 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.033365-0
Loading
/content/journal/jgv/10.1099/vir.0.033365-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error