1887

Abstract

Chronic wasting disease (CWD) is an emergent prion disease spreading in cervid populations in North America, South Korea and Scandinavia. Rapid detection of CWD prions shed by live animals using minimally invasive methods remains an important need. Previous studies in deer, elk and hamsters have demonstrated prion replication in the nasal olfactory mucosa, yet the temporal profile of CWD prion shedding in nasal secretions has not been well characterized. Here we report nasal prion shedding in 18 deer orally exposed to low doses of CWD prions and monitored longitudinally by several parameters. Serially collected nasal swabs were assayed for CWD prion seeding activity using iron oxide magnetic extraction and real-time quaking-induced conversion (IOME RT-QuIC). These findings were correlated with the results from longitudinal tonsil biopsies, terminal tissues and PRNP genotype. We detected nasal prion shedding 3–16 months after the first positive tonsil biopsy in ten of the 18 deer; detectable shedding persisted thereafter in nine of the ten animals. Surprisingly, nasal swabs were negative in eight deer, even though all were CWD-infected as determined by tonsil biopsies and terminal tissue assays. Nasal shedding was detected more often in deer that were homozygous for glycine at codon 96, and those that were near or demonstrating symptoms of clinical disease shed earlier and more frequently, irrespective of prion exposure dose. The results of this study demonstrate nasal shedding of CWD prions that can be detected using minimally invasive nasal swab sampling and RT-QuIC analysis.

Funding
This study was supported by the:
  • National Institute of Neurological Disorders and Stroke (Award R01-AI112956-06)
    • Principle Award Recipient: K. MathiasonCandace
  • National Institute of Neurological Disorders and Stroke (Award PO1-AI077774)
    • Principle Award Recipient: A. HooverEdward
  • National Institute of Neurological Disorders and Stroke (Award RO1-NS061902-09R)
    • Principle Award Recipient: A. HooverEdward
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001825
2023-01-27
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/104/1/jgv001825.html?itemId=/content/journal/jgv/10.1099/jgv.0.001825&mimeType=html&fmt=ahah

References

  1. Williams ES, Young S. Chronic wasting disease of captive mule deer: a spongiform encephalopathy. J Wildl Dis 1980; 16:89–98 [View Article] [PubMed]
    [Google Scholar]
  2. Safar JG, Lessard P, Tamgüney G, Freyman Y, Deering C et al. Transmission and detection of prions in feces. J Infect Dis 2008; 198:81–89 [View Article] [PubMed]
    [Google Scholar]
  3. John TR, Schätzl HM, Gilch S. Early detection of chronic wasting disease prions in urine of pre-symptomatic deer by real-time quaking-induced conversion assay. Prion 2013; 7:253–258 [View Article]
    [Google Scholar]
  4. Mathiason CK, Powers JG, Dahmes SJ, Osborn DA, Miller KV et al. Infectious prions in the saliva and blood of deer with chronic wasting disease. Science 2006; 314:133–136 [View Article] [PubMed]
    [Google Scholar]
  5. Bessen RA, Shearin H, Martinka S, Boharski R, Lowe D et al. Prion shedding from olfactory neurons into nasal secretions. PLoS Pathog 2010; 6:e1000837 [View Article] [PubMed]
    [Google Scholar]
  6. Haley NJ, Siepker C, Hoon-Hanks LL, Mitchell G, Walter WD et al. Seeded amplification of chronic wasting disease prions in nasal brushings and recto-anal mucosa-associated lymphoid tissues from elk by real-time quaking-induced conversion. J Clin Microbiol 2016; 54:1117–1126 [View Article]
    [Google Scholar]
  7. Haley NJ, Siepker C, Walter WD, Thomsen BV, Greenlee JJ et al. Antemortem detection of chronic wasting disease prions in nasal brush collections and rectal biopsy specimens from white-tailed deer by real-time quaking-induced conversion. J Clin Microbiol 2016; 54:1108–1116 [View Article]
    [Google Scholar]
  8. Atarashi R, Sano K, Satoh K, Nishida N. Real-time quaking-induced conversion: a highly sensitive assay for prion detection. Prion 2011; 5:150–153 [View Article] [PubMed]
    [Google Scholar]
  9. Henderson DM, Manca M, Haley NJ, Denkers ND, Nalls AV et al. Rapid antemortem detection of CWD prions in deer saliva. PLoS One 2013; 8:e74377 [View Article] [PubMed]
    [Google Scholar]
  10. Denkers ND, Henderson DM, Mathiason CK, Hoover EA. Enhanced prion detection in biological samples by magnetic particle extraction and real-time quaking-induced conversion. J Gen Virol 2016; 97:2023–2029 [View Article]
    [Google Scholar]
  11. Henderson DM, Tennant JM, Haley NJ, Denkers ND, Mathiason CK et al. Detection of chronic wasting disease prion seeding activity in deer and elk feces by real-time quaking-induced conversion. J Gen Virol 2017; 98:1953–1962 [View Article]
    [Google Scholar]
  12. Ferreira NC, Charco JM, Plagenz J, Orru CD, Denkers ND et al. Detection of chronic wasting disease in mule and white-tailed deer by RT-QuIC analysis of outer ear. Sci Rep 2021; 11:7702 [View Article] [PubMed]
    [Google Scholar]
  13. McNulty EE, Nalls AV, Xun R, Denkers ND, Hoover EA et al. In vitro detection of haematogenous prions in white-tailed deer orally dosed with low concentrations of chronic wasting disease. J Gen Virol 2020; 101:347–361 [View Article]
    [Google Scholar]
  14. Henderson DM, Denkers ND, Hoover CE, McNulty EE, Cooper SK et al. Progression of chronic wasting disease in white-tailed deer analyzed by serial biopsy RT-QuIC and immunohistochemistry. PLoS One 2020; 15:e0228327 [View Article] [PubMed]
    [Google Scholar]
  15. Denkers ND, Hoover CE, Davenport KA, Henderson DM, McNulty EE et al. Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease. PLoS One 2020; 15:e0237410 [View Article] [PubMed]
    [Google Scholar]
  16. Denkers ND, Hayes-Klug J, Anderson KR, Seelig DM, Haley NJ et al. Aerosol transmission of chronic wasting disease in white-tailed deer. J Virol 2013; 87:1890–1892 [View Article] [PubMed]
    [Google Scholar]
  17. Wilham JM, Orrú CD, Bessen RA, Atarashi R, Sano K et al. Rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays. PLoS Pathog 2010; 6:e1001217 [View Article] [PubMed]
    [Google Scholar]
  18. Henderson DM, Davenport KA, Haley NJ, Denkers ND, Mathiason CK et al. Quantitative assessment of prion infectivity in tissues and body fluids by real-time quaking-induced conversion. J Gen Virol 2015; 96:210–219 [View Article]
    [Google Scholar]
  19. Bloodgood J, Kiupel M, Melotti J, Straka K. Chronic wasting disease diagnostic discrepancies: the importance of testing both Medial retropharyngeal lymph nodes. J Wildl Dis 2021; 57:194–198 [View Article]
    [Google Scholar]
  20. Schwabenlander MD, Rowden GR, Li M, LaSharr K, Hildebrand EC et al. Comparison of chronic wasting disease detection methods and procedures: implications for free-ranging white-tailed deer (Odocoileus virginianus) surveillance and management. J Wildl Dis 2022; 58:50–62 [View Article]
    [Google Scholar]
  21. Davenport KA, Mosher BA, Brost BM, Henderson DM, Denkers ND et al. Assessment of chronic wasting disease prion shedding in deer saliva with occupancy modeling. J Clin Microbiol 2018; 56:e01243-17 [View Article]
    [Google Scholar]
  22. Henderson DM, Denkers ND, Hoover CE, Garbino N, Mathiason CK et al. Longitudinal detection of prion shedding in saliva and urine by chronic wasting disease-infected deer by real-time quaking-induced conversion. J Virol 2015; 89:9338–9347 [View Article]
    [Google Scholar]
  23. Orrú CD, Bongianni M, Tonoli G, Ferrari S, Hughson AG et al. A test for Creutzfeldt-Jakob disease using nasal brushings. N Engl J Med 2014; 371:519–529 [View Article] [PubMed]
    [Google Scholar]
  24. Zanusso G, Monaco S, Pocchiari M, Caughey B. Advanced tests for early and accurate diagnosis of Creutzfeldt-Jakob disease. Nat Rev Neurol 2016; 12:325–333 [View Article] [PubMed]
    [Google Scholar]
  25. Orrú CD, Groveman BR, Foutz A, Bongianni M, Cardone F et al. Ring trial of 2nd generation RT-QuIC diagnostic tests for sporadic CJD. Ann Clin Transl Neurol 2020; 7:2262–2271 [View Article] [PubMed]
    [Google Scholar]
  26. De Luca CMG, Elia AE, Portaleone SM, Cazzaniga FA, Rossi M et al. Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson’s disease and multiple system atrophy. Transl Neurodegener 2019; 8:24 [View Article] [PubMed]
    [Google Scholar]
  27. Sbriccoli M, Cardone F, Valanzano A, Lu M, Graziano S et al. Neuroinvasion of the 263K scrapie strain after intranasal administration occurs through olfactory-unrelated pathways. Acta Neuropathol 2009; 117:175–184 [View Article] [PubMed]
    [Google Scholar]
  28. Keane DP, Barr DJ, Keller JE, Hall SM, Langenberg JA et al. 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 2008; 20:58–60 [View Article]
    [Google Scholar]
  29. Spraker TR, Balachandran A, Zhuang D, O’Rourke KI. Variable patterns of distribution of PrP(CWD) in the obex and cranial lymphoid tissues of Rocky Mountain elk (Cervus elaphus nelsoni) with subclinical chronic wasting disease. Vet Rec 2004; 155:295–302 [View Article]
    [Google Scholar]
  30. Moya KL, Hässig R, Créminon C, Laffont I, Di Giamberardino L. Enhanced detection and retrograde axonal transport of PrPc in peripheral nerve. J Neurochem 2004; 88:155–160 [View Article] [PubMed]
    [Google Scholar]
  31. Spraker TR, Zink RR, Cummings BA, Sigurdson CJ, Miller MW et al. Distribution of protease-resistant prion protein and spongiform encephalopathy in free-ranging mule deer (Odocoileus hemionus) with chronic wasting disease. Vet Pathol 2002; 39:546–556 [View Article]
    [Google Scholar]
  32. DeJoia C, Moreaux B, O’Connell K, Bessen RA. Prion infection of oral and nasal mucosa. J Virol 2006; 80:4546–4556 [View Article] [PubMed]
    [Google Scholar]
  33. Plummer IH, Wright SD, Johnson CJ, Pedersen JA, Samuel MD. Temporal patterns of chronic wasting disease prion excretion in three cervid species. J Gen Virol 2017; 98:1932–1942 [View Article] [PubMed]
    [Google Scholar]
  34. Hoover CE, Davenport KA, Henderson DM, Denkers ND, Mathiason CK et al. Pathways of prion spread during early chronic wasting disease in deer. J Virol 2017; 91:10 [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001825
Loading
/content/journal/jgv/10.1099/jgv.0.001825
Loading

Data & Media loading...

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