1887

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Volume 93, Issue 5

Sensitivity of protein misfolding cyclic amplification versus immunohistochemistry in ante-mortem detection of chronic wasting disease Free

Abstract

As the only prion disease affecting free-ranging animals, ante-mortem identification of affected cervids has become paramount in understanding chronic wasting disease (CWD) pathogenesis, prevalence and control of horizontal or vertical transmission. To seek maximal sensitivity in ante-mortem detection of CWD infection, this study used paired tonsil biopsy samples collected at various time points from 48 CWD-exposed cervids to compare blinded serial protein misfolding cyclic amplification (sPMCA) with the assay long considered the ‘gold standard’ for CWD detection, immunohistochemistry (IHC). sPMCA-negative controls (34 % of the samples evaluated) included tissues from mock-inoculated animals and unspiked negative controls, all of which tested negative throughout the course of the study. It was found that sPMCA on tonsil biopsies detected CWD infection significantly earlier (2.78 months, 95 % confidence interval 2.40–3.15) than conventional IHC. Interestingly, a correlation was observed between early detection by sPMCA and host genotype. These findings demonstrate that -amplification assays provide enhanced sensitivity and advanced detection of CWD infection in the peripheral tissues of cervids, with a potential role for spike or substrate genotype in sPMCA amplification efficiency.

  • Received:
  • Accepted:
  • Published Online:
© 2012 SGM
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2012-05-01
2024-04-20
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References

  1. Almberg E. S., Cross P. C., Johnson C. J., Heisey D. M., Richards B. J. 2011; Modeling routes of chronic wasting disease transmission: environmental prion persistence promotes deer population decline and extinction. PLoS ONE 6:e19896 [View Article][PubMed]
     [Google Scholar]
  2. Angers R. C., Seward T. S., Napier D., Green M., Hoover E., Spraker T., O’Rourke K., Balachandran A., Telling G. C. 2009; Chronic wasting disease prions in elk antler velvet. Emerg Infect Dis 15:696–703 [View Article][PubMed]
     [Google Scholar]
  3. 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]
  4. 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]
  5. Browning S. R., Mason G. L., Seward T., Green M., Eliason G. A., Mathiason C., Miller M. W., Williams E. S., Hoover E., Telling G. C. 2004; Transmission of prions from mule deer and elk with chronic wasting disease to transgenic mice expressing cervid PrP. J Virol 78:13345–13350 [View Article][PubMed]
     [Google Scholar]
  6. Bucalossi C., Cosseddu G., D’Agostino C., Di Bari M. A., Chiappini B., Conte M., Rosone F., De Grossi L., Scavia G. other authors 2011; Assessment of the genetic susceptibility of sheep to scrapie by protein misfolding cyclic amplification and comparison with experimental scrapie transmission studies. J Virol 85:8386–8392 [View Article][PubMed]
     [Google Scholar]
  7. Castilla J., Saá P., Soto C. 2005; Detection of prions in blood. Nat Med 11:982–985[PubMed]
     [Google Scholar]
  8. Clewley J. P., Kelly C. M., Andrews N., Vogliqi K., Mallinson G., Kaisar M., Hilton D. A., Ironside J. W., Edwards P. other authors 2009; Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey. BMJ 338:b1442 [View Article][PubMed]
     [Google Scholar]
  9. Dennis M. M., Thomsen B. V., Marshall K. L., Hall S. M., Wagner B. A., Salman M. D., Norden D. K., Gaiser C., Sutton D. L. 2009; Evaluation of immunohistochemical detection of prion protein in rectoanal mucosa-associated lymphoid tissue for diagnosis of scrapie in sheep. Am J Vet Res 70:63–72 [View Article][PubMed]
     [Google Scholar]
  10. Frosh A., Smith L. C., Jackson C. J., Linehan J. M., Brandner S., Wadsworth J. D., Collinge J. 2004; Analysis of 2000 consecutive UK tonsillectomy specimens for disease-related prion protein. Lancet 364:1260–1262 [View Article][PubMed]
     [Google Scholar]
  11. González L., Dagleish M. P., Bellworthy S. J., Sisó S., Stack M. J., Chaplin M. J., Davis L. A., Hawkins S. A., Hughes J., Jeffrey M. 2006; Postmortem diagnosis of preclinical and clinical scrapie in sheep by the detection of disease-associated PrP in their rectal mucosa. Vet Rec 158:325–331 [View Article][PubMed]
     [Google Scholar]
  12. Gough K. C., Baker C. A., Rees H. C., Terry L. A., Spiropoulos J., Thorne L., Maddison B. C. 2012; The oral secretion of infectious scrapie prions occurs in preclinical sheep with a range of PRNP genotypes. J Virol 86:566–571[PubMed] [CrossRef]
     [Google Scholar]
  13. Haley N. J., Mathiason C. K., Zabel M. D., Telling G. C., Hoover E. A. 2009a; Detection of sub-clinical CWD infection in conventional test-negative deer long after oral exposure to urine and feces from CWD+ deer. PLoS ONE 4:e7990 [View Article][PubMed]
     [Google Scholar]
  14. Haley N. J., Seelig D. M., Zabel M. D., Telling G. C., Hoover E. A. 2009b; Detection of CWD prions in urine and saliva of deer by transgenic mouse bioassay. PLoS ONE 4:e4848 [View Article][PubMed]
     [Google Scholar]
  15. Haley N. J., Mathiason C. K., Carver S., Zabel M., Telling G. C., Hoover E. A. 2011; Detection of chronic wasting disease prions in salivary, urinary, and intestinal tissues of deer: potential mechanisms of prion shedding and transmission. J Virol 85:6309–6318 [View Article][PubMed]
     [Google Scholar]
  16. Hibler C. P., Wilson K. L., Spraker T. R., Miller M. W., Zink R. R., DeBuse L. L., Andersen E., Schweitzer D., Kennedy J. A. other authors 2003; Field validation and assessment of an enzyme-linked immunosorbent assay for detecting chronic wasting disease in mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni). J Vet Diagn Invest 15:311–319 [View Article][PubMed]
     [Google Scholar]
  17. Hill A. F., Zeidler M., Ironside J., Collinge J. 1997; Diagnosis of new variant Creutzfeldt–Jakob disease by tonsil biopsy. Lancet 349:99–100 [View Article][PubMed]
     [Google Scholar]
  18. Hill A. F., Butterworth R. J., Joiner S., Jackson G., Rossor M. N., Thomas D. J., Frosh A., Tolley N., Bell J. E. other authors 1999; Investigation of variant Creutzfeldt–Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 353:183–189 [View Article][PubMed]
     [Google Scholar]
  19. Hunter N., Goldmann W., Foster J. D., Cairns D., Smith G. 1997; Natural scrapie and PrP genotype: case–control studies in British sheep. Vet Rec 141:137–140 [View Article][PubMed]
     [Google Scholar]
  20. International Society for Infectious Diseases 2010; Chronic wasting disease, cervids – USA (03): (Missouri). http://www.promedmail.org/direct.php?id=20100303.0697
  21. International Society for Infectious Diseases 2011; Chronic wasting disease, cervid - USA (05): (Maryland). http://www.promedmail.org/direct.php?id=20110212.0486
  22. Johnson C., Johnson J., Vanderloo J. P., Keane D., Aiken J. M., McKenzie D. 2006; Prion protein polymorphisms in white-tailed deer influence susceptibility to chronic wasting disease. J Gen Virol 87:2109–2114 [View Article][PubMed]
     [Google Scholar]
  23. Keane D. P., Barr D. J., Bochsler P. N., Hall S. M., Gidlewski T., O’Rourke K. I., Spraker T. R., Samuel M. D. 2008a; Chronic wasting disease in a Wisconsin white-tailed deer farm. J Vet Diagn Invest 20:698–703 [View Article][PubMed]
     [Google Scholar]
  24. Keane D. P., Barr D. J., Keller J. E., Hall S. M., Langenberg J. A., Bochsler P. N. 2008b; Comparison of retropharyngeal lymph node and obex region of the brainstem in detection of chronic wasting disease in white-tailed deer (Odocoileus virginianus). J Vet Diagn Invest 20:58–60 [View Article][PubMed]
     [Google Scholar]
  25. Kurt T. D., Telling G. C., Zabel M. D., Hoover E. A. 2009; Trans-species amplification of PrPCWD and correlation with rigid loop 170N. Virology 387:235–243 [View Article][PubMed]
     [Google Scholar]
  26. Landis J. R., Koch G. G. 1977; The measurement of observer agreement for categorical data. Biometrics 33:159–174 [View Article][PubMed]
     [Google Scholar]
  27. 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. other authors 2006; Infectious prions in the saliva and blood of deer with chronic wasting disease. Science 314:133–136 [View Article][PubMed]
     [Google Scholar]
  28. Mathiason C. K., Hays S. A., Powers J., Hayes-Klug J., Langenberg J., Dahmes S. J., Osborn D. A., Miller K. V., Warren R. J. other authors 2009; Infectious prions in pre-clinical deer and transmission of chronic wasting disease solely by environmental exposure. PLoS ONE 4:e5916 [View Article][PubMed]
     [Google Scholar]
  29. Mathiason C. K., Hayes-Klug J., Hays S. A., Powers J., Osborn D. A., Dahmes S. J., Miller K. V., Warren R. J., Mason G. L. other authors 2010; B cells and platelets harbor prion infectivity in the blood of deer infected with chronic wasting disease. J Virol 84:5097–5107 [View Article][PubMed]
     [Google Scholar]
  30. Meyerett C., Michel B., Pulford B., Spraker T. R., Nichols T. A., Johnson T., Kurt T., Hoover E. A., Telling G. C., Zabel M. D. 2008; In vitro strain adaptation of CWD prions by serial protein misfolding cyclic amplification. Virology 382:267–276 [View Article][PubMed]
     [Google Scholar]
  31. Miller M. W., Wild M. A., Williams E. S. 1998; Epidemiology of chronic wasting disease in captive Rocky Mountain elk. J Wildl Dis 34:532–538[PubMed] [CrossRef]
     [Google Scholar]
  32. Miller M. W., Hobbs N. T., Tavener S. J. 2006; Dynamics of prion disease transmission in mule deer. Ecol Appl 16:2208–2214 [View Article][PubMed]
     [Google Scholar]
  33. National Wildlife Health Centre 2011; Chronic wasting disease (CWD). http://www.nwhc.usgs.gov/disease_information/chronic_wasting_disease/
  34. O’Rourke K. I., Baszler T. V., Besser T. E., Miller J. M., Cutlip R. C., Wells G. A., Ryder S. J., Parish S. M., Hamir A. N. other authors 2000; Preclinical diagnosis of scrapie by immunohistochemistry of third eyelid lymphoid tissue. J Clin Microbiol 38:3254–3259[PubMed]
     [Google Scholar]
  35. O’Rourke K. I., Zhuang D., Lyda A., Gomez G., Williams E. S., Tuo W., Miller M. W. 2003; Abundant PrP(CWD) in tonsil from mule deer with preclinical chronic wasting disease. J Vet Diagn Invest 15:320–323 [View Article][PubMed]
     [Google Scholar]
  36. OIE 2010; Chapter 2.4.6. Bovine spongiform encephalopathy. In OIE Terrestrial Manual 2010 pp. 1–12 http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.04.06_BSE.pdf
     [Google Scholar]
  37. 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]
  38. Peters J., Miller J. M., Jenny A. L., Peterson T. L., Carmichael K. P. 2000; Immunohistochemical diagnosis of chronic wasting disease in preclinically affected elk from a captive herd. J Vet Diagn Invest 12:579–582 [View Article][PubMed]
     [Google Scholar]
  39. Saborio G. P., Permanne B., Soto C. 2001; Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411:810–813 [View Article][PubMed]
     [Google Scholar]
  40. Safar J. G., Scott M., Monaghan J., Deering C., Didorenko S., Vergara J., Ball H., Legname G., Leclerc E. other authors 2002; Measuring prions causing bovine spongiform encephalopathy or chronic wasting disease by immunoassays and transgenic mice. Nat Biotechnol 20:1147–1150 [View Article][PubMed]
     [Google Scholar]
  41. Safar J. G., Geschwind M. D., Deering C., Didorenko S., Sattavat M., Sanchez H., Serban A., Vey M., Baron H. other authors 2005; Diagnosis of human prion disease. Proc Natl Acad Sci U S A 102:3501–3506 [View Article][PubMed]
     [Google Scholar]
  42. Sigurdson C. J. 2008; A prion disease of cervids: chronic wasting disease. Vet Res 39:41 [View Article][PubMed]
     [Google Scholar]
  43. Sigurdson C. J., Williams E. S., Miller M. W., Spraker T. R., O’Rourke K. I., Hoover E. A. 1999; Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus). J Gen Virol 80:2757–2764[PubMed]
     [Google Scholar]
  44. Sohn H.-J., Kim J.-H., Choi K.-S., Nah J.-J., Joo Y.-S., Jean Y.-H., Ahn S.-W., Kim O.-K., Kim D.-Y., Balachandran A. 2002; A case of chronic wasting disease in an elk imported to Korea from Canada. J Vet Med Sci 64:855–858 [View Article][PubMed]
     [Google Scholar]
  45. Soto C., Anderes L., Suardi S., Cardone F., Castilla J., Frossard M. J., Peano S., Saa P., Limido L., Carbonatto M. 2005; Pre-symptomatic detection of prions by cyclic amplification of protein misfolding. FEBS Lett 579:638–642 [View Article][PubMed]
     [Google Scholar]
  46. Spraker T. R., Miller M. W., Williams E. S., Getzy D. M., Adrian W. J., Schoonveld G. G., Spowart R. A., O’Rourke K. I., Miller J. M., Merz P. A. 1997; Spongiform encephalopathy in free-ranging mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus) and Rocky Mountain elk (Cervus elaphus nelsoni) in northcentral Colorado. J Wildl Dis 33:1–6[PubMed] [CrossRef]
     [Google Scholar]
  47. Spraker T. R., O’Rourke K. I., Balachandran A., Zink R. R., Cummings B. A., Miller M. W., Powers B. E. 2002; Validation of monoclonal antibody F99/97.6.1 for immunohistochemical staining of brain and tonsil in mule deer (Odocoileus hemionus) with chronic wasting disease. J Vet Diagn Invest 14:3–7 [View Article][PubMed]
     [Google Scholar]
  48. Spraker T. R., Balachandran A., Zhuang D., O’Rourke K. I. 2004; Variable patterns of distribution of PrPCWD in the obex and cranial lymphoid tissues of Rocky Mountain elk (Cervus elaphus nelsoni) with subclinical chronic wasting disease. Vet Rec 155:295–302 [View Article][PubMed]
     [Google Scholar]
  49. Spraker T. R., Gidlewski T. L., Balachandran A., VerCauteren K. C., Creekmore L., Munger R. D. 2006; Detection of PrPCWD in postmortem rectal lymphoid tissues in Rocky Mountain elk (Cervus elaphus nelsoni) infected with chronic wasting disease. J Vet Diagn Invest 18:553–557 [View Article][PubMed]
     [Google Scholar]
  50. 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. Nature 461:529–532 Corrigendum Nature 466:653 [View Article][PubMed]
     [Google Scholar]
  51. Thackray A. M., Hopkins L., Bujdoso R. 2007; Proteinase K-sensitive disease-associated ovine prion protein revealed by conformation-dependent immunoassay. Biochem J 401:475–483 [View Article][PubMed]
     [Google Scholar]
  52. USDA 2011; Chronic wasting disease. http://www.aphis.usda.gov/animal_health/animal_diseases/cwd/
  53. van Keulen L. J., Schreuder B. E., Meloen R. H., Mooij-Harkes G., Vromans M. E., Langeveld J. P. 1996; Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie. J Clin Microbiol 34:1228–1231[PubMed]
     [Google Scholar]
  54. 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]
  55. Williams E. S. 2005; Chronic wasting disease. Vet Pathol 42:530–549 [View Article][PubMed]
     [Google Scholar]
  56. Williams E. S., Young S. 1980; Chronic wasting disease of captive mule deer: a spongiform encephalopathy. J Wildl Dis 16:89–98[PubMed] [CrossRef]
     [Google Scholar]
  57. Williams E. S., Young S. 1982; Spongiform encephalopathy of Rocky Mountain elk. J Wildl Dis 18:465–471[PubMed] [CrossRef]
     [Google Scholar]
  58. Windl O., Dempster M., Estibeiro J. P., Lathe R., de Silva R., Esmonde T., Will R., Springbett A., Campbell T. A. other authors 1996; Genetic basis of Creutzfeldt–Jakob disease in the United Kingdom: a systematic analysis of predisposing mutations and allelic variation in the PRNP gene. Hum Genet 98:259–264 [View Article][PubMed]
     [Google Scholar]
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Sensitivity of protein misfolding cyclic amplification versus immunohistochemistry in ante-mortem detection of chronic wasting disease
J. Gen. Virol. 93, 1141 (2012); https://doi.org/10.1099/vir.0.039073-0
/content/journal/jgv/10.1099/vir.0.039073-0
/content/journal/jgv/10.1099/vir.0.039073-0
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