1887

Abstract

Prions have been demonstrated in body fluids and excreta using bioassay, but at levels too low for detection by conventional direct-detection assays. More rapid and sensitive detection of prions in these clinically accessible specimens would be valuable for diagnosis and investigations of transmission, environmental impact, and interventions. In addition to very low concentrations of prions, amplification assays are challenged by the presence of inhibitors in these complex sources. Here, we leverage the prion attribute of avid metal binding with the versatile power of real-time quaking-induced conversion (RT-QuIC) to enhance and simplify detection of chronic wasting-disease prions in biological samples. Iron oxide particle binding and magnetic extraction combined with RT-QuIC permitted rapid analysis of the low concentrations of prions in saliva, urine, faeces, and cerebrospinal fluid. These methods are pertinent to ante-mortem detection, monitoring, and surveillance, and could conceivably be applicable to other protein-misfolding disorders.

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2016-08-01
2019-12-15
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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 Methods4:645–650 [CrossRef][PubMed]
    [Google Scholar]
  2. Bernoulli C., Siegfried J., Baumgartner G., Regli F., Rabinowicz T., Gajdusek D. C., Gibbs C. J., Jr.. 1977; Danger of accidental person-to-person transmission of Creutzfeldt-Jakob disease by surgery. Lancet1:478–479[PubMed][CrossRef]
    [Google Scholar]
  3. Brown D. R., Qin K., Herms J. W., Madlung A., Manson J., Strome R., Fraser P. E., Kruck T., von Bohlen A. et al. 1997; The cellular prion protein binds copper in vivo . Nature390:684–687 [CrossRef][PubMed]
    [Google Scholar]
  4. Chen B., Morales R., Barria M. A., Soto C.. 2010; Estimating prion concentration in fluids and tissues by quantitative PMCA. Nat Methods7:519–520 [CrossRef][PubMed]
    [Google Scholar]
  5. Denkers N. D., Hayes-Klug J., Anderson K. R., Seelig D. M., Haley N. J., Dahmes S. J., Osborn D. A., Miller K. V., Warren R. J. et al. 2013; Aerosol transmission of chronic wasting disease in white-tailed deer. J Virol87:1890–1892 [CrossRef][PubMed]
    [Google Scholar]
  6. Edgeworth J. A., Farmer M., Sicilia A., Tavares P., Beck J., Campbell T., Lowe J., Mead S., Rudge P. et al. 2011; Detection of prion infection in variant Creutzfeldt-Jakob disease: a blood-based assay. Lancet377:487–493 [CrossRef][PubMed]
    [Google Scholar]
  7. Elder A. M., Henderson D. M., Nalls A. V., Hoover E. A., Kincaid A. E., Bartz J. C., Mathiason C. K.. 2015; Immediate and ongoing detection of prions in the blood of hamsters and deer following oral, nasal, or blood inoculations. J Virol89:7421–7424 [CrossRef][PubMed]
    [Google Scholar]
  8. Elder A. M., Henderson D. M., Nalls A. V., Wilham J. M., Caughey B. W., Hoover E. A., Kincaid A. E., Bartz J. C., Mathiason C. K.. 2013; In vitro detection of prionemia in TSE-infected cervids and hamsters. PLoS One8:e80203 [CrossRef][PubMed]
    [Google Scholar]
  9. Gibbs C. J., Asher D. M., Kobrine A., Amyx H. L., Sulima M. P., Gajdusek D. C.. 1994; Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery. J Neurol Neurosurg Psychiatry57:757–758 [CrossRef][PubMed]
    [Google Scholar]
  10. Goñi F., Mathiason C. K., Yim L., Wong K., Hayes-Klug J., Nalls A., Peyser D., Estevez V., Denkers N. et al. 2015; Mucosal immunization with an attenuated Salmonella vaccine partially protects white-tailed deer from chronic wasting disease. Vaccine33:726–733 [CrossRef][PubMed]
    [Google Scholar]
  11. Gonzalez-Romero D., Barria M. A., Leon P., Morales R., Soto C.. 2008; Detection of infectious prions in urine. FEBS Lett582:3161–3166 [CrossRef][PubMed]
    [Google Scholar]
  12. Haley N. J., Mathiason C. K., Zabel M. D., Telling G. C., Hoover E. A.. 2009; Detection of sub-clinical CWD infection in conventional test-negative deer long after oral exposure to urine and feces from CWD+ deer. PLoS One4:e7990 [CrossRef][PubMed]
    [Google Scholar]
  13. Haley N. J., Van de Motter A., Carver S., Henderson D., Davenport K., Seelig D. M., Mathiason C., Hoover E.. 2013; Prion-seeding activity in cerebrospinal fluid of deer with chronic wasting disease. PLoS One8:e81488 [CrossRef][PubMed]
    [Google Scholar]
  14. Henderson D. M., Davenport K. A., Haley N. J., Denkers N. D., Mathiason C. K., Hoover E. A.. 2015a; Quantitative assessment of prion infectivity in tissues and body fluids by real-time quaking-induced conversion. J Gen Virol96:210–219 [CrossRef]
    [Google Scholar]
  15. Henderson D. M., Denkers N. D., Hoover C. E., Garbino N., Mathiason C. K., Hoover E. A.. 2015b; Longitudinal detection of prion shedding in saliva and urine by chronic wasting disease-infected deer by real-time quaking-induced conversion. J Virol89:9338–9347 [CrossRef][PubMed]
    [Google Scholar]
  16. Henderson D. M., Manca M., Haley N. J., Denkers N. D., Nalls A. V., Mathiason C. K., Caughey B., Hoover E. A.. 2013; Rapid antemortem detection of CWD prions in deer saliva. PLoS One8:e74377 [CrossRef][PubMed]
    [Google Scholar]
  17. Hornshaw M. P., McDermott J. R., Candy J. M.. 1995; Copper binding to the N-terminal tandem repeat regions of mammalian and avian prion protein. Biochem Biophys Res Commun207:621–629 [CrossRef][PubMed]
    [Google Scholar]
  18. Krüger D., Thomzig A., Lenz G., Kampf K., McBride P., Beekes M.. 2009; Faecal shedding, alimentary clearance and intestinal spread of prions in hamsters fed with scrapie. Vet Res40:4 [CrossRef][PubMed]
    [Google Scholar]
  19. Lim K., Kim S. Y., Lee B., Segarra C., Kang S., Ju Y., Schmerr M. J., Coste J., Kim S. Y. 2015; Magnetic microparticle-based multimer detection system for the detection of prion oligomers in sheep. Int J Nanomedicine10:241–250 [CrossRef][PubMed]
    [Google Scholar]
  20. Mathiason C. K., Powers J. G., Dahmes S. J., Osborn D. A., Miller K. V., Warren R. J., Mason G. L., Hays S. A., Hayes-Klug J. et al. 2006; Infectious prions in the saliva and blood of deer with chronic wasting disease. Science314:133–136 [CrossRef][PubMed]
    [Google Scholar]
  21. Miller M. B., Supattapone S.. 2011; Superparamagnetic nanoparticle capture of prions for amplification. J Virol85:2813–2817 [CrossRef][PubMed]
    [Google Scholar]
  22. Miller M. W., Williams E. S.. 2002; Detection of PrP(CWD) in mule deer by immunohistochemistry of lymphoid tissues. Vet Rec151:610–612 [CrossRef][PubMed]
    [Google Scholar]
  23. Müller-Schiffmann A., Petsch B., Leliveld S. R., Muyrers J., Salwierz A., Mangels C., Schwarzinger S., Riesner D., Stitz L., Korth C.. 2009; Complementarity determining regions of an anti-prion protein scFv fragment orchestrate conformation specificity and antiprion activity. Mol Immunol46:532–540 [CrossRef][PubMed]
    [Google Scholar]
  24. Orrú C. D., Bongianni M., Tonoli G., Ferrari S., Hughson A. G., Groveman B. R., Fiorini M., Pocchiari M., Monaco S. et al. 2014; A test for Creutzfeldt-Jakob disease using nasal brushings. N Engl J Med371:519–529 [CrossRef][PubMed]
    [Google Scholar]
  25. 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. MBio2:e00078-11 [CrossRef][PubMed]
    [Google Scholar]
  26. Pulford B., Spraker T. R., Wyckoff A. C., Meyerett C., Bender H., Ferguson A., Wyatt B., Lockwood K., Powers J. et al. 2012; Detection of PrPCWD in feces from naturally exposed Rocky Mountain elk (Cervus elaphus nelsoni) using protein misfolding cyclic amplification. J Wildl Dis48:425–434 [CrossRef][PubMed]
    [Google Scholar]
  27. Saborio G. P., Permanne B., Soto C.. 2001; Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature411:810–813 [CrossRef]
    [Google Scholar]
  28. Safar J. G., Lessard P., Tamgüney G., Freyman Y., Deering C., Letessier F., Dearmond S. J., Prusiner S. B.. 2008; Transmission and detection of prions in feces. J Infect Dis198:81–89 [CrossRef][PubMed]
    [Google Scholar]
  29. Sigurdson C. J., Spraker T. R., Miller M. W., Oesch B., Hoover E. A.. 2001; PrP(CWD) in the myenteric plexus, vagosympathetic trunk and endocrine glands of deer with chronic wasting disease. J Gen Virol82:2327–2334 [CrossRef][PubMed]
    [Google Scholar]
  30. Spraker T. R., Zink R. R., Cummings B. A., Wild M. A., Miller M. W., O'Rourke K. I.. 2002; Comparison of histological lesions and immunohistochemical staining of proteinase-resistant prion protein in a naturally occurring spongiform encephalopathy of free-ranging mule deer (Odocoileus hemionus) with those of chronic wasting disease of captive mule deer. Vet Pathol39:110–119[PubMed][CrossRef]
    [Google Scholar]
  31. Tamgüney G., Miller M. W., Wolfe L. L., Sirochman T. M., Glidden D. V., Palmer C., Lemus A., DeArmond S. J., Prusiner S. B.. 2009; Asymptomatic deer excrete infectious prions in faeces. Nature461:529–532 [CrossRef][PubMed]
    [Google Scholar]
  32. Tamgüney G., Richt J. A., Hamir A. N., Greenlee J. J., Miller M. W., Wolfe L. L., Sirochman T. M., Young A. J., Glidden D. V. et al. 2012; Salivary prions in sheep and deer. Prion6:52–61 [CrossRef][PubMed]
    [Google Scholar]
  33. Van Keulen L. J., Schreuder B. E., Meloen R. H., Mooij-Harkes G., Vromans M. E., Langeveld J. P., Langeveld J. P.. 1996; Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie. J Clin Microbiol34:1228–1231[PubMed]
    [Google Scholar]
  34. Wadsworth J. D., Joiner S., Hill A. F., Campbell T. A., Desbruslais M., Luthert P. J., Collinge J.. 2001; Tissue distribution of protease resistant prion protein in variant Creutzfeldt-Jakob disease using a highly sensitive immunoblotting assay. Lancet358:171–180 [CrossRef][PubMed]
    [Google Scholar]
  35. Zobeley E., Flechsig E., Cozzio A., Enari M., Weissmann C.. 1999; Infectivity of scrapie prions bound to a stainless steel surface. Mol Med5:240–243[PubMed]
    [Google Scholar]
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