1887

Abstract

The prevalence, host range and geographical bounds of chronic wasting disease (CWD), the prion disease of cervids, are expanding. Horizontal transmission likely contributes the majority of new CWD cases, but the mechanism by which prions are transmitted among CWD-affected cervids remains unclear. To address the extent to which prion amplification in peripheral tissues contributes to contagious transmission, we assessed the prion levels in central nervous and lymphoreticular system tissues in white-tailed deer (Odocoileus virginianus), red deer (Cervus elaphus elaphus) and elk (Cervus canadensis). Using real-time quaking-induced conversion, cervid prion cell assay and transgenic mouse bioassay, we found that the retropharyngeal lymph nodes of red deer, white-tailed deer and elk contained similar prion titres to brain from the same individuals. We propose that marked lymphotropism is essential for the horizontal transmission of prion diseases and postulate that shed CWD prions are produced in the periphery.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001053
2018-03-26
2019-09-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/99/5/753.html?itemId=/content/journal/jgv/10.1099/jgv.0.001053&mimeType=html&fmt=ahah

References

  1. Will RG, Ironside JW, Zeidler M, Estibeiro K, Cousens SN et al. A new variant of Creutzfeldt-Jakob disease in the UK. The Lancet 1996;347:921–925 [CrossRef]
    [Google Scholar]
  2. Cohen FE, Prusiner SB. Pathologic conformations of prion proteins. Annu Rev Biochem 1998;67:793–819 [CrossRef][PubMed]
    [Google Scholar]
  3. Monello RJ, Powers JG, Hobbs NT, Spraker TR, O'Rourke KI et al. Efficacy of antemortem rectal biopsies to diagnose and estimate prevalence of chronic wasting disease in free-ranging cow elk (Cervus elaphus nelsoni). J Wildl Dis 2013;49:270–278 [CrossRef][PubMed]
    [Google Scholar]
  4. Miller MW, Williams ES, Hobbs NT, Wolfe LL. Environmental sources of prion transmission in mule deer. Emerg Infect Dis 2004;10:1003–1006 [CrossRef][PubMed]
    [Google Scholar]
  5. Collee JG, Bradley R. BSE: a decade on–Part 2. Lancet 1997;349:715–721 [CrossRef][PubMed]
    [Google Scholar]
  6. Sigurdson CJ, Williams ES, Miller MW, Spraker TR, O'Rourke KI et al. Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus). J Gen Virol 1999;80:2757–2764 [CrossRef][PubMed]
    [Google Scholar]
  7. 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:e00077-17 [CrossRef][PubMed]
    [Google Scholar]
  8. 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 [CrossRef][PubMed]
    [Google Scholar]
  9. Fox KA, Jewell JE, Williams ES, Miller MW. Patterns of PrPCWD accumulation during the course of chronic wasting disease infection in orally inoculated mule deer (Odocoileus hemionus). J Gen Virol 2006;87:3451–3461 [CrossRef][PubMed]
    [Google Scholar]
  10. Miller MW, Williams ES. Detection of PrPCWD in mule deer by immunohistochemistry of lymphoid tissues. Vet Rec 2002;151:610–612 [CrossRef][PubMed]
    [Google Scholar]
  11. Race BL, Meade-White KD, Ward A, Jewell J, Miller MW et al. Levels of abnormal prion protein in deer and elk with chronic wasting disease. Emerg Infect Dis 2007;13:824–829 [CrossRef][PubMed]
    [Google Scholar]
  12. Angers RC, Browning SR, Seward TS, Sigurdson CJ, Miller MW et al. Prions in skeletal muscles of deer with chronic wasting disease. Science 2006;311:1117 [CrossRef][PubMed]
    [Google Scholar]
  13. Race B, Meade-White K, Oldstone MB, Race R, Chesebro B. Detection of prion infectivity in fat tissues of scrapie-infected mice. PLoS Pathog 2008;4:e1000232 [CrossRef][PubMed]
    [Google Scholar]
  14. Sigurdson CJ, Spraker TR, Miller MW, Oesch B, Hoover EA. PrPCWD in the myenteric plexus, vagosympathetic trunk and endocrine glands of deer with chronic wasting disease. J Gen Virol 2001;82:2327–2334 [CrossRef][PubMed]
    [Google Scholar]
  15. Jewell JE, Brown J, Kreeger T, Williams ES. Prion protein in cardiac muscle of elk (Cervus elaphus nelsoni) and white-tailed deer (Odocoileus virginianus) infected with chronic wasting disease. J Gen Virol 2006;87:3443–3450 [CrossRef][PubMed]
    [Google Scholar]
  16. Balachandran A, Harrington NP, Algire J, Soutyrine A, Spraker TR et al. Experimental oral transmission of chronic wasting disease to red deer (Cervus elaphus elaphus): early detection and late stage distribution of protease-resistant prion protein. Can Vet J 2010;51:169–178[PubMed]
    [Google Scholar]
  17. Haley NJ, Mathiason CK, Carver S, Zabel M, Telling GC et al. Detection of chronic wasting disease prions in salivary, urinary, and intestinal tissues of deer: potential mechanisms of prion shedding and transmission. J Virol 2011;85:6309–6318 [CrossRef][PubMed]
    [Google Scholar]
  18. Davenport KA, Hoover CE, Bian J, Telling GC, Mathiason CK et al. PrPC expression and prion seeding activity in the alimentary tract and lymphoid tissue of deer. PLoS One 2017;12:e0183927 [CrossRef][PubMed]
    [Google Scholar]
  19. Andréoletti O, Berthon P, Marc D, Sarradin P, Grosclaude J et al. Early accumulation of PrPSc in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie. J Gen Virol 2000;81:3115–3126 [CrossRef][PubMed]
    [Google Scholar]
  20. van Keulen LJ, Schreuder BE, Vromans ME, Langeveld JP, Smits MA. Scrapie-associated prion protein in the gastrointestinal tract of sheep with natural scrapie. J Comp Pathol 1999;121:55–63 [CrossRef][PubMed]
    [Google Scholar]
  21. Jeffrey M, Begara-McGorum I, Clark S, Martin S, Clark J et al. Occurrence and distribution of infection-specific PrP in tissues of clinical scrapie cases and cull sheep from scrapie-affected farms in Shetland. J Comp Pathol 2002;127:264–273 [CrossRef][PubMed]
    [Google Scholar]
  22. Heggebø R, Press CM, Gunnes G, González L, Jeffrey M. Distribution and accumulation of PrP in gut-associated and peripheral lymphoid tissue of scrapie-affected Suffolk sheep. J Gen Virol 2002;83:479–489 [CrossRef][PubMed]
    [Google Scholar]
  23. Jeffrey M, Martin S, Thomson JR, Dingwall WS, Begara-McGorum I et al. Onset and distribution of tissue PrP accumulation in scrapie-affected suffolk sheep as demonstrated by sequential necropsies and tonsillar biopsies. J Comp Pathol 2001;125:48–57 [CrossRef][PubMed]
    [Google Scholar]
  24. Race R, Jenny A, Sutton D. Scrapie infectivity and proteinase K—resistant prion protein in sheep placenta, brain, spleen, and lymph node: implications for transmission and antemortem diagnosis. J Infect Dis 1998;178:949–953 [CrossRef][PubMed]
    [Google Scholar]
  25. Balkema-Buschmann A, Eiden M, Hoffmann C, Kaatz M, Ziegler U et al. BSE infectivity in the absence of detectable PrPSc accumulation in the tongue and nasal mucosa of terminally diseased cattle. J Gen Virol 2011;92:467–476 [CrossRef][PubMed]
    [Google Scholar]
  26. Hoffmann C, Eiden M, Kaatz M, Keller M, Ziegler U et al. BSE infectivity in jejunum, ileum and ileocaecal junction of incubating cattle. Vet Res 2011;42:21 [CrossRef][PubMed]
    [Google Scholar]
  27. Balkema-Buschmann A, Fast C, Kaatz M, Eiden M, Ziegler U et al. Pathogenesis of classical and atypical BSE in cattle. Prev Vet Med 2011;102:112–117 [CrossRef]
    [Google Scholar]
  28. Wells GA, Spiropoulos J, Hawkins SA, Ryder SJ. Pathogenesis of experimental bovine spongiform encephalopathy: preclinical infectivity in tonsil and observations on the distribution of lingual tonsil in slaughtered cattle. Vet Rec 2005;156:401–407 [CrossRef][PubMed]
    [Google Scholar]
  29. 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 [CrossRef][PubMed]
    [Google Scholar]
  30. Atarashi R, Wilham JM, Christensen L, Hughson AG, Moore RA et al. Simplified ultrasensitive prion detection by recombinant PrP conversion with shaking. Nat Methods 2008;5:211–212 [CrossRef][PubMed]
    [Google Scholar]
  31. Bian J, Napier D, Khaychuck V, Angers R, Graham C et al. Cell-based quantification of chronic wasting disease prions. J Virol 2010;84:8322–8326 [CrossRef][PubMed]
    [Google Scholar]
  32. Browning SR, Mason GL, Seward T, Green M, Eliason GA et al. Transmission of prions from mule deer and elk with chronic wasting disease to transgenic mice expressing cervid PrP. J Virol 2004;78:13345–13350 [CrossRef][PubMed]
    [Google Scholar]
  33. 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 [CrossRef][PubMed]
    [Google Scholar]
  34. Bian J, Kang HE, Telling GC. Quinacrine promotes replication and conformational mutation of chronic wasting disease prions. Proc Natl Acad Sci USA 2014;111:6028–6033 [CrossRef][PubMed]
    [Google Scholar]
  35. Bian J, Khaychuk V, Angers RC, Fernández-Borges N, Vidal E et al. Prion replication without host adaptation during interspecies transmissions. Proc Natl Acad Sci USA 2017;114:1141–1146 [CrossRef][PubMed]
    [Google Scholar]
  36. Williamson RA, Peretz D, Pinilla C, Ball H, Bastidas RB et al. Mapping the prion protein using recombinant antibodies. J Virol 1998;72:9413–9418[PubMed]
    [Google Scholar]
  37. Angers RC, Kang HE, Napier D, Browning S, Seward T et al. Prion strain mutation determined by prion protein conformational compatibility and primary structure. Science 2010;328:1154–1158 [CrossRef][PubMed]
    [Google Scholar]
  38. Williams ES, Young S. Chronic wasting disease of captive mule deer: a spongiform encephalopathy. J Wildl Dis 1980;16:89–98 [CrossRef][PubMed]
    [Google Scholar]
  39. Benestad SL, Mitchell G, Simmons M, Ytrehus B, Vikøren T. First case of chronic wasting disease in Europe in a Norwegian free-ranging reindeer. Vet Res 2016;47:1–7 [CrossRef]
    [Google Scholar]
  40. van Keulen LJ, Vromans ME, van Zijderveld FG. Early and late pathogenesis of natural scrapie infection in sheep. APMIS 2002;110:23–32 [CrossRef][PubMed]
    [Google Scholar]
  41. Cutlip RC, Miller JM, Race RE, Jenny AL, Katz JB et al. Intracerebral transmission of scrapie to cattle. J Infect Dis 1994;169:814–820 [CrossRef][PubMed]
    [Google Scholar]
  42. Haley NJ, Siepker C, Greenlee JJ, Richt JA. Limited amplification of chronic wasting disease prions in the peripheral tissues of intracerebrally inoculated cattle. J Gen Virol 2016;97:1720–1724 [CrossRef][PubMed]
    [Google Scholar]
  43. Foster JD, Bruce M, McConnell I, Chree A, Fraser H. Detection of BSE infectivity in brain and spleen of experimentally infected sheep. Vet Rec 1996;138:546–548 [CrossRef][PubMed]
    [Google Scholar]
  44. Foster JD, Parnham D, Chong A, Goldmann W, Hunter N. Clinical signs, histopathology and genetics of experimental transmission of BSE and natural scrapie to sheep and goats. Vet Rec 2001;148:165–171 [CrossRef][PubMed]
    [Google Scholar]
  45. Béringue V, Herzog L, Jaumain E, Reine F, Sibille P et al. Facilitated cross-species transmission of prions in extraneural tissue. Science 2012;335:472–475 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001053
Loading
/content/journal/jgv/10.1099/jgv.0.001053
Loading

Data & Media loading...

Most Cited This Month

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