1887

Abstract

Chronic wasting disease (CWD) of cervids is almost certainly transmitted by mucosal contact with the causative prion, whether by direct (animal-to-animal) or indirect (environmental) means. Yet the sites and mechanisms of prion entry remain to be further understood. This study sought to extend this understanding by demonstrating that ferrets exposed to CWD via several mucosal routes developed infection, CWD prion protein (PrP) amplification in lymphoid tissues, neural invasion and florid transmissible spongiform encephalopathy lesions resembling those in native cervid hosts. The ferrets developed extensive PrP accumulation in the nervous system, retina and olfactory epithelium, with lesser deposition in tongue, muscle, salivary gland and the vomeronasal organ. PrP accumulation in mucosal sites, including upper respiratory tract epithelium, olfactory epithelium and intestinal Peyer’s patches, make the shedding of prions by infected ferrets plausible. It was also observed that regionally targeted exposure of the nasopharyngeal mucosa resulted in an increased attack rate when compared with oral exposure. The latter finding suggests that nasal exposure enhances permissiveness to CWD infection. The ferret model has further potential for investigation of portals for initiation of CWD infection.

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2013-02-01
2024-12-06
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References

  1. Andréoletti O., Berthon P., Marc D., Sarradin P., Grosclaude J., van Keulen L., Schelcher F., Elsen J. M., Lantier F. 2000; Early accumulation of PrPSc in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie. J Gen Virol 81:3115–3126[PubMed]
    [Google Scholar]
  2. Angers R. C., Browning S. R., Seward T. S., Sigurdson C. J., Miller M. W., Hoover E. A., Telling G. C. 2006; Prions in skeletal muscles of deer with chronic wasting disease. Science 311:1117 [View Article][PubMed]
    [Google Scholar]
  3. 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]
  4. Baeten L. A., Powers B. E., Jewell J. E., Spraker T. R., Miller M. W. 2007; A natural case of chronic wasting disease in a free-ranging moose (Alces alces shirasi). J Wildl Dis 43:309–314[PubMed] [CrossRef]
    [Google Scholar]
  5. Bartz J. C., Marsh R. F., McKenzie D. I., Aiken J. M. 1998; The host range of chronic wasting disease is altered on passage in ferrets. Virology 251:297–301 [View Article][PubMed]
    [Google Scholar]
  6. Bartz J. C., Dejoia C., Tucker T., Kincaid A. E., Bessen R. A. 2005; Extraneural prion neuroinvasion without lymphoreticular system infection. J Virol 79:11858–11863 [View Article][PubMed]
    [Google Scholar]
  7. Bessen R. A., Shearin H., Martinka S., Boharski R., Lowe D., Wilham J. M., Caughey B., Wiley J. A. 2010; Prion shedding from olfactory neurons into nasal secretions. PLoS Pathog 6:e1000837 [View Article][PubMed]
    [Google Scholar]
  8. Bessen R. A., Wilham J. M., Lowe D., Watschke C. P., Shearin H., Martinka S., Caughey B., Wiley J. A. 2012; Accelerated shedding of prions following damage to the olfactory epithelium. J Virol 86:1777–1788 [View Article][PubMed]
    [Google Scholar]
  9. Carp R. I. 1982; Transmission of scrapie by oral route: effect of gingival scarification. Lancet 319:170–171 [View Article][PubMed]
    [Google Scholar]
  10. Corona C., Porcario C., Martucci F., Iulini B., Manea B., Gallo M., Palmitessa C., Maurella C., Mazza M. other authors 2009; Olfactory system involvement in natural scrapie disease. J Virol 83:3657–3667 [View Article][PubMed]
    [Google Scholar]
  11. DeJoia C., Moreaux B., O’Connell K., Bessen R. A. 2006; Prion infection of oral and nasal mucosa. J Virol 80:4546–4556 [View Article][PubMed]
    [Google Scholar]
  12. Denkers N. D., Seelig D. M., Telling G. C., Hoover E. A. 2010; Aerosol and nasal transmission of chronic wasting disease in cervidized mice. J Gen Virol 91:1651–1658 [View Article][PubMed]
    [Google Scholar]
  13. Denkers N. D., Telling G. C., Hoover E. A. 2011; Minor oral lesions facilitate transmission of chronic wasting disease. J Virol 85:1396–1399 [View Article][PubMed]
    [Google Scholar]
  14. Dennis B. J., Kerr D. I. 1975; Olfactory bulb connections with basal rhinencephalon in the ferret: an evoked potential and neuroanatomical study. J Comp Neurol 159:129–148 [View Article][PubMed]
    [Google Scholar]
  15. 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]
  16. 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]
  17. Hamir A. N., Kunkle R. A., Cutlip R. C., Miller J. M., O’Rourke K. I., Williams E. S., Miller M. W., Stack M. J., Chaplin M. J., Richt J. A. 2005; Experimental transmission of chronic wasting disease agent from mule deer to cattle by the intracerebral route. J Vet Diagn Invest 17:276–281 [View Article][PubMed]
    [Google Scholar]
  18. Hamir A. N., Kunkle R. A., Cutlip R. C., Miller J. M., Williams E. S., Richt J. A. 2006; Transmission of chronic wasting disease of mule deer to Suffolk sheep following intracerebral inoculation. J Vet Diagn Invest 18:558–565 [View Article][PubMed]
    [Google Scholar]
  19. Haybaeck J., Heikenwalder M., Klevenz B., Schwarz P., Margalith I., Bridel C., Mertz K., Zirdum E., Petsch B. other authors 2011; Aerosols transmit prions to immunocompetent and immunodeficient mice. PLoS Pathog 7:e1001257 [View Article][PubMed]
    [Google Scholar]
  20. Heisey D. M., Mickelsen N. A., Schneider J. R., Johnson C. J., Johnson C. J., Langenberg J. A., Bochsler P. N., Keane D. P., Barr D. J. 2010; Chronic wasting disease (CWD) susceptibility of several North American rodents that are sympatric with cervid CWD epidemics. J Virol 84:210–215 [View Article][PubMed]
    [Google Scholar]
  21. Kim T.-Y., Shon H.-J., Joo Y.-S., Mun U.-K., Kang K.-S., Lee Y.-S. 2005; Additional cases of chronic wasting disease in imported deer in Korea. J Vet Med Sci 67:753–759 [View Article][PubMed]
    [Google Scholar]
  22. Kincaid A. E., Bartz J. C. 2007; The nasal cavity is a route for prion infection in hamsters. J Virol 81:4482–4491 [View Article][PubMed]
    [Google Scholar]
  23. Kincaid A. E., Hudson K. F., Richey M. W., Bartz J. C. 2012; Rapid transepithelial transport of prions following inhalation. J Virol 86:12731–12740 [View Article][PubMed]
    [Google Scholar]
  24. 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 [CrossRef]
    [Google Scholar]
  25. Kurt T. D., Seelig D. M., Schneider J. R., Johnson C. J., Telling G. C., Heisey D. M., Hoover E. A. 2011; Alteration of the chronic wasting disease species barrier by in vitro prion amplification. J Virol 85:8528–8537 [View Article][PubMed]
    [Google Scholar]
  26. Liu W. G., Brown D. A., Fraser J. R. 2003; Immunohistochemical comparison of anti-prion protein (PrP) antibodies in the CNS of mice infected with scrapie. J Histochem Cytochem 51:1065–1071 [View Article][PubMed]
    [Google Scholar]
  27. Maignien T., Lasmézas C. I., Beringue V., Dormont D., Deslys J. P. 1999; Pathogenesis of the oral route of infection of mice with scrapie and bovine spongiform encephalopathy agents. J Gen Virol 80:3035–3042[PubMed]
    [Google Scholar]
  28. Marsh R. F., Kincaid A. E., Bessen R. A., Bartz J. C. 2005; Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiri sciureus). J Virol 79:13794–13796 [View Article][PubMed]
    [Google Scholar]
  29. 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]
  30. McLean I. W., Nakane P. K. 1974; Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. J Histochem Cytochem 22:1077–1083 [View Article][PubMed]
    [Google Scholar]
  31. Moya K. L., Hässig R., Créminon C., Laffont I., Di Giamberardino L. 2004; Enhanced detection and retrograde axonal transport of PrPc in peripheral nerve. J Neurochem 88:155–160 [View Article][PubMed]
    [Google Scholar]
  32. O’Rourke K. I., Zhuang D., Lyda A., Gomez G., Williams E. S., Tuo W., Miller M. W. 2003; Abundant PrPCWD in tonsil from mule deer with preclinical chronic wasting disease. J Vet Diagn Invest 15:320–323 [View Article][PubMed]
    [Google Scholar]
  33. Perrott M. R., Sigurdson C. J., Mason G. L., Hoover E. A. 2012; Evidence for distinct chronic wasting disease (CWD) strains in experimental CWD in ferrets. J Gen Virol 93:212–221 [View Article][PubMed]
    [Google Scholar]
  34. Race B., Meade-White K. D., Miller M. W., Barbian K. D., Rubenstein R., LaFauci G., Cervenakova L., Favara C., Gardner D. other authors 2009; Susceptibilities of nonhuman primates to chronic wasting disease. Emerg Infect Dis 15:1366–1376 [View Article][PubMed]
    [Google Scholar]
  35. Raymond G. J., Raymond L. D., Meade-White K. D., Hughson A. G., Favara C., Gardner D., Williams E. S., Miller M. W., Race R. E., Caughey B. 2007; Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains. J Virol 81:4305–4314 [View Article][PubMed]
    [Google Scholar]
  36. Sbriccoli M., Cardone F., Valanzano A., Lu M., Graziano S., De Pascalis A., Ingrosso L., Zanusso G., Monaco S. other authors 2009; Neuroinvasion of the 263K scrapie strain after intranasal administration occurs through olfactory-unrelated pathways. Acta Neuropathol 117:175–184 [View Article][PubMed]
    [Google Scholar]
  37. Schuler K. L., Jenks J. A., DePerno C. S., Wild M. A., Swanson C. C. 2005; Tonsillar biopsy test for chronic wasting disease: two sampling approaches in mule deer and white-tailed deer. J Wildl Dis 41:820–824[PubMed] [CrossRef]
    [Google Scholar]
  38. Sigurdson C. J. 2008; A prion disease of cervids: chronic wasting disease. Vet Res 39:41 [View Article][PubMed]
    [Google Scholar]
  39. 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]
  40. Sigurdson C. J., Spraker T. R., Miller M. W., Oesch B., Hoover E. A. 2001; PrPCWD in the myenteric plexus, vagosympathetic trunk and endocrine glands of deer with chronic wasting disease. J Gen Virol 82:2327–2334[PubMed]
    [Google Scholar]
  41. Sigurdson C. J., Barillas-Mury C., Miller M. W., Oesch B., van Keulen L. J., Langeveld J. P., Hoover E. A. 2002; PrPCWD lymphoid cell targets in early and advanced chronic wasting disease of mule deer. J Gen Virol 83:2617–2628[PubMed]
    [Google Scholar]
  42. Sigurdson C. J., Mathiason C. K., Perrott M. R., Eliason G. A., Spraker T. R., Glatzel M., Manco G., Bartz J. C., Miller M. W., Hoover E. A. 2008; Experimental chronic wasting disease (CWD) in the ferret. J Comp Pathol 138:189–196 [View Article][PubMed]
    [Google Scholar]
  43. 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]
  44. 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]
  45. Spraker T. R., Zink R. R., Cummings B. A., Sigurdson C. J., Miller M. W., O’Rourke K. I. 2002a; Distribution of protease-resistant prion protein and spongiform encephalopathy in free-ranging mule deer (Odocoileus hemionus) with chronic wasting disease. Vet Pathol 39:546–556 [View Article][PubMed]
    [Google Scholar]
  46. Spraker T. R., Zink R. R., Cummings B. A., Wild M. A., Miller M. W., O’Rourke K. I. 2002b; 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 Pathol 39:110–119 [View Article][PubMed]
    [Google Scholar]
  47. Spraker T. R., O’Rourke K. I., Balachandran A., Zink R. R., Cummings B. A., Miller M. W., Powers B. E. 2002c; 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. 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. Lancet 358:171–180 [View Article][PubMed]
    [Google Scholar]
  49. Wild M. A., Spraker T. R., Sigurdson C. J., O’Rourke K. I., Miller M. W. 2002; Preclinical diagnosis of chronic wasting disease in captive mule deer (Odocoileus hemionus) and white-tailed deer (Odocoileus virginianus) using tonsillar biopsy. J Gen Virol 83:2629–2634[PubMed]
    [Google Scholar]
  50. Williams E. S. 2005; Chronic wasting disease. Vet Pathol 42:530–549 [View Article][PubMed]
    [Google Scholar]
  51. Williams E. S., Miller M. W. 2002; Chronic wasting disease in deer and elk in North America. Rev Sci Tech 21:305–316[PubMed]
    [Google Scholar]
  52. 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]
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