1887

Abstract

Chronic wasting disease (CWD) is a transmissible, fatal prion disease of cervids and is largely confined to North America. The origin of CWD continues to pose a conundrum: does the disease arise spontaneously or result from some other naturally occurring reservoir? To address whether prions from sheep might be able to cause disease in cervids, we inoculated mice expressing the elk prion protein (PrP) transgene [Tg(ElkPrP) mice] with two scrapie prion isolates. The SSBP/1 scrapie isolate transmitted disease to Tg(ElkPrP) mice with a median incubation time of 270 days, but a second isolate failed to produce neurological dysfunction in these mice. Although prions from cattle with bovine spongiform encephalopathy (BSE) did not transmit to the Tg(ElkPrP) mice, they did transmit after being passaged through sheep. In Tg(ElkPrP) mice, the sheep-passaged BSE prions exhibited an incubation time of approximately 300 days. SSBP/1 prions produced abundant deposits of the disease-causing PrP isoform, denoted PrP, in the cerebellum and pons of Tg(ElkPrP) mice, whereas PrP accumulation in Tg mice inoculated with sheep-passaged BSE prions was confined to the deep cerebellar nuclei, habenula and the brainstem. The susceptibility of ‘cervidized’ mice to ‘ovinized’ prions raises the question about why CWD has not been reported in other parts of the world where cervids and scrapie-infected sheep coexist.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.007500-0
2009-04-01
2019-11-13
Loading full text...

Full text loading...

/deliver/fulltext/jgv/90/4/1035.html?itemId=/content/journal/jgv/10.1099/vir.0.007500-0&mimeType=html&fmt=ahah

References

  1. 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 [CrossRef]
    [Google Scholar]
  2. 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.[CrossRef]
    [Google Scholar]
  3. Belay, E. D., Maddox, R. A., Williams, E. S., Miller, M. W., Gambetti, P. & Schonberger, L. B. ( 2004; ). Chronic wasting disease and potential transmission to humans. Emerg Infect Dis 10, 977–984.[CrossRef]
    [Google Scholar]
  4. Brookmeyer, R. & Crowley, J. ( 1982; ). A confidence interval for the median survival time. Biometrics 38, 29–41.[CrossRef]
    [Google Scholar]
  5. Bruce, M. E. & Fraser, H. ( 1991; ). Scrapie strain variation and its implications. Curr Top Microbiol Immunol 172, 125–138.
    [Google Scholar]
  6. Büeler, H., Fisher, M., Lang, Y., Bluethmann, H., Lipp, H.-P., DeArmond, S. J., Prusiner, S. B., Aguet, M. & Weissmann, C. ( 1992; ). Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 356, 577–582.[CrossRef]
    [Google Scholar]
  7. Carlson, G. A., Goodman, P. A., Lovett, M., Taylor, B. A., Marshall, S. T., Peterson-Torchia, M., Westaway, D. & Prusiner, S. B. ( 1988; ). Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time. Mol Cell Biol 8, 5528–5540.
    [Google Scholar]
  8. Carlson, G. A., Ebeling, C., Yang, S.-L., Telling, G., Torchia, M., Groth, D., Westaway, D., DeArmond, S. J. & Prusiner, S. B. ( 1994; ). Prion isolate specified allotypic interactions between the cellular and scrapie prion proteins in congenic and transgenic mice. Proc Natl Acad Sci U S A 91, 5690–5694.[CrossRef]
    [Google Scholar]
  9. Chandler, R. L. ( 1961; ). Encephalopathy in mice produced by inoculation with scrapie brain material. Lancet 1, 1378–1379.
    [Google Scholar]
  10. Conner, M. M., Miller, M. W., Ebinger, M. R. & Burnham, K. P. ( 2007; ). A meta-BACI approach for evaluating management intervention on chronic wasting disease in mule deer. Ecol Appl 17, 140–153.[CrossRef]
    [Google Scholar]
  11. Dagleish, M. P., Martin, S., Steele, P., Finlayson, J., Siso, S., Hamilton, S., Chianini, F., Reid, H. W., Gonzalez, L. & Jeffrey, M. ( 2008; ). Experimental transmission of bovine spongiform encephalopathy to European red deer (Cervus elaphus elaphus). BMC Vet Res 4, 17 [CrossRef]
    [Google Scholar]
  12. De Bosschere, H., Saegerman, C., Neukermans, A., Berkvens, D., Casaer, J., Vanopdenbosch, E. & Roels, S. ( 2006; ). First chronic wasting disease (CWD) surveillance of roe deer (Capreolus capreolus) in the northern part of Belgium. Vet Q 28, 55–60.
    [Google Scholar]
  13. Dickinson, A. G. & Outram, G. W. ( 1988; ). Genetic aspects of unconventional virus infections: the basis of the virino hypothesis. Ciba Found Symp 135, 63–83.
    [Google Scholar]
  14. Dube, C., Mehren, K. G., Barker, I. K., Peart, B. L. & Balachandran, A. ( 2006; ). Retrospective investigation of chronic wasting disease of cervids at the Toronto Zoo, 1973–2003. Can Vet J 47, 1185–1193.
    [Google Scholar]
  15. Foster, J. D., Hope, J. & Fraser, H. ( 1993; ). Transmission of bovine spongiform encephalopathy to sheep and goats. Vet Rec 133, 339–341.[CrossRef]
    [Google Scholar]
  16. Fraser, H. & Dickinson, A. G. ( 1973; ). Scrapie in mice. Agent-strain differences in the distribution and intensity of grey matter vacuolation. J Comp Pathol 83, 29–40.[CrossRef]
    [Google Scholar]
  17. Goldmann, W., Hunter, N., Smith, G., Foster, J. & Hope, J. ( 1994; ). PrP genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie. J Gen Virol 75, 989–995.[CrossRef]
    [Google Scholar]
  18. Goldmann, W., Martin, T., Foster, J., Hughes, S., Smith, G., Hughes, K., Dawson, M. & Hunter, N. ( 1996; ). Novel polymorphisms in the caprine PrP gene: a codon 142 mutation associated with scrapie incubation period. J Gen Virol 77, 2885–2891.[CrossRef]
    [Google Scholar]
  19. Green, K. M., Browning, S. R., Seward, T. S., Jewell, J. E., Ross, D. L., Green, M. A., Williams, E. S., Hoover, E. A. & Telling, G. C. ( 2008; ). The elk PRNP codon 132 polymorphism controls cervid and scrapie prion propagation. J Gen Virol 89, 598–608.[CrossRef]
    [Google Scholar]
  20. Hamir, A. N., Miller, J. M., Cutlip, R. C., Kunkle, R. A., Jenny, A. L., Stack, M. J., Chaplin, M. J. & Richt, J. A. ( 2004; ). Transmission of sheep scrapie to elk (Cervus elaphus nelsoni) by intracerebral inoculation: final outcome of the experiment. J Vet Diagn Invest 16, 316–321.[CrossRef]
    [Google Scholar]
  21. 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.[CrossRef]
    [Google Scholar]
  22. Hamir, A. N., Miller, J. M., Kunkle, R. A., Hall, S. M. & Richt, J. A. ( 2007; ). Susceptibility of cattle to first-passage intracerebral inoculation with chronic wasting disease agent from white-tailed deer. Vet Pathol 44, 487–493.[CrossRef]
    [Google Scholar]
  23. Hourrigan, J., Klingsporn, A., Clark, W. W. & de Camp, M. ( 1979; ). Epidemiology of scrapie in the United States. In Slow Transmissible Diseases of the Nervous System, vol. 1, pp. 331–356. Edited by S. B. Prusiner & W. J. Hadlow. New York: Academic Press.
  24. Hunter, N. ( 2007; ). Scrapie: uncertainties, biology and molecular approaches. Biochim Biophys Acta 1772, 619–628.[CrossRef]
    [Google Scholar]
  25. Kaplan, E. L. & Meier, P. ( 1958; ). Nonparametric estimation from incomplete observations. J Am Stat Assoc 53, 457–481.[CrossRef]
    [Google Scholar]
  26. Kataoka, N., Nishimura, M., Horiuchi, M. & Ishiguro, N. ( 2005; ). Surveillance of chronic wasting disease in sika deer, Cervus nippon, from Tokachi district in Hokkaido. J Vet Med Sci 67, 349–351.[CrossRef]
    [Google Scholar]
  27. 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.[CrossRef]
    [Google Scholar]
  28. Kimberlin, R. H., Cole, S. & Walker, C. A. ( 1987; ). Temporary and permanent modifications to a single strain of mouse scrapie on transmission to rats and hamsters. J Gen Virol 68, 1875–1881.[CrossRef]
    [Google Scholar]
  29. Kimberlin, R. H., Walker, C. A. & Fraser, H. ( 1989; ). The genomic identity of different strains of mouse scrapie is expressed in hamsters and preserved on reisolation in mice. J Gen Virol 70, 2017–2025.[CrossRef]
    [Google Scholar]
  30. Kong, Q., Huang, S., Zou, W., Vanegas, D., Wang, M., Wu, D., Yuan, J., Zheng, M., Bai, H. & other authors ( 2005; ). Chronic wasting disease of elk: transmissibility to humans examined by transgenic mouse models. J Neurosci 25, 7944–7999.[CrossRef]
    [Google Scholar]
  31. Laemmli, U. K. ( 1970; ). Cleavage of structural proteins during the assembly of the head of bacteriophage T-4. Nature 227, 680–685.[CrossRef]
    [Google Scholar]
  32. Marsh, R. F., Bessen, R. A., Lehmann, S. & Hartsough, G. R. ( 1991; ). Epidemiological and experimental studies on a new incident of transmissible mink encephalopathy. J Gen Virol 72, 589–594.[CrossRef]
    [Google Scholar]
  33. 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.[CrossRef]
    [Google Scholar]
  34. MaWhinney, S., Pape, W. J., Forster, J. E., Anderson, C. A., Bosque, P. & Miller, M. W. ( 2006; ). Human prion disease and relative risk associated with chronic wasting disease. Emerg Infect Dis 12, 1527–1535.[CrossRef]
    [Google Scholar]
  35. Miller, M. W. & Williams, E. S. ( 2003; ). Prion disease: horizontal prion transmission in mule deer. Nature 425, 35–36.[CrossRef]
    [Google Scholar]
  36. Muramoto, T., Kitamoto, T., Tateishi, J. & Goto, I. ( 1992; ). The sequential development of abnormal prion protein accumulation in mice with Creutzfeldt–Jakob disease. Am J Pathol 140, 1411–1420.
    [Google Scholar]
  37. Muramoto, T., DeArmond, S. J., Scott, M., Telling, G. C., Cohen, F. E. & Prusiner, S. B. ( 1997; ). Heritable disorder resembling neuronal storage disease in mice expressing prion protein with deletion of an α-helix. Nat Med 3, 750–755.[CrossRef]
    [Google Scholar]
  38. O'Rourke, K. I., Besser, T. E., Miller, M. W., Cline, T. F., Spraker, T. R., Jenny, A. L., Wild, M. A., Zebarth, G. L. & Williams, E. S. ( 1999; ). PrP genotypes of captive and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease. J Gen Virol 80, 2765–2769.
    [Google Scholar]
  39. Pan, K.-M., Baldwin, M., Nguyen, J., Gasset, M., Serban, A., Groth, D., Mehlhorn, I., Huang, Z., Fletterick, R. J. & other authors ( 1993; ). Conversion of α-helices into β-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci U S A 90, 10962–10966.[CrossRef]
    [Google Scholar]
  40. Peretz, D., Williamson, R. A., Kaneko, K., Vergara, J., Leclerc, E., Schmitt-Ulms, G., Mehlhorn, I. R., Legname, G., Wormald, M. R. & other authors ( 2001; ). Antibodies inhibit prion propagation and clear cell cultures of prion infectivity. Nature 412, 739–743.[CrossRef]
    [Google Scholar]
  41. Peretz, D., Williamson, R. A., Legname, G., Matsunaga, Y., Vergara, J., Burton, D., DeArmond, S. J., Prusiner, S. B. & Scott, M. R. ( 2002; ). A change in the conformation of prions accompanies the emergence of a new prion strain. Neuron 34, 921–932.[CrossRef]
    [Google Scholar]
  42. Prusiner, S. B. ( 2007; ). Prions. In Fields Virology, 5th edn, pp. 3059–3092. Edited by D. M. Knipe, P. M. Howley, D. E. Griffin, R. A. Lamb, M. A. Martin, B. Roizman & S. E. Straus. Philadelphia, PA: Lippincott Williams & Wilkins.
  43. Raymond, G. J., Bossers, A., Raymond, L. D., O'Rourke, K. I., McHolland, L. E., Bryant, P. K., III, Miller, M. W., Williams, E. S., Smits, M. & Caughey, B. ( 2000; ). Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease. EMBO J 19, 4425–4430.[CrossRef]
    [Google Scholar]
  44. Richt, J. A., Kunkle, R. A., Alt, D., Nicholson, E. M., Hamir, A. N., Czub, S., Kluge, J., Davis, A. J. & Hall, S. M. ( 2007; ). Identification and characterization of two bovine spongiform encephalopathy cases diagnosed in the United States. J Vet Diagn Invest 19, 142–154.[CrossRef]
    [Google Scholar]
  45. Safar, J., Wille, H., Itri, V., Groth, D., Serban, H., Torchia, M., Cohen, F. E. & Prusiner, S. B. ( 1998; ). Eight prion strains have PrPSc molecules with different conformations. Nat Med 4, 1157–1165.[CrossRef]
    [Google Scholar]
  46. 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.[CrossRef]
    [Google Scholar]
  47. 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.[CrossRef]
    [Google Scholar]
  48. Samuel, M. D. ( 2007; ). Chronic wasting disease in Wisconsin white-tailed deer: is there a practical solution? In Pre-Prion 2007 Chronic Wasting Disease Workshop, Edinburgh, UK, September 2007, p. P2.
  49. Schettler, E., Steinbach, F., Eschenbacher-Kaps, I., Gerst, K., Muessdoerffer, F., Risch, K., Streich, W. J. & Frolich, K. ( 2006; ). Surveillance for prion disease in cervids, Germany. Emerg Infect Dis 12, 319–322.[CrossRef]
    [Google Scholar]
  50. Schwaiger, K., Stierstorfer, B., Schmahl, W. & Bauer, J. ( 2004; ). The occurrence of transmissible spongiform encephalopathies in roe deer (Capreolus capreolus), red deer (Cervus elaphus) and chamois (Rupicapra rupicapra) in Bavaria. Berl Munch Tierarztl Wochenschr 117, 24–29 (in German).
    [Google Scholar]
  51. Scott, M., Foster, D., Mirenda, C., Serban, D., Coufal, F., Wälchli, M., Torchia, M., Groth, D., Carlson, G. & other authors ( 1989; ). Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques. Cell 59, 847–857.[CrossRef]
    [Google Scholar]
  52. Scott, M. R., Köhler, R., Foster, D. & Prusiner, S. B. ( 1992; ). Chimeric prion protein expression in cultured cells and transgenic mice. Protein Sci 1, 986–997.[CrossRef]
    [Google Scholar]
  53. Scott, M., Groth, D., Foster, D., Torchia, M., Yang, S.-L., DeArmond, S. J. & Prusiner, S. B. ( 1993; ). Propagation of prions with artificial properties in transgenic mice expressing chimeric PrP genes. Cell 73, 979–988.[CrossRef]
    [Google Scholar]
  54. Scott, M. R., Safar, J., Telling, G., Nguyen, O., Groth, D., Torchia, M., Koehler, R., Tremblay, P., Walther, D. & other authors ( 1997; ). Identification of a prion protein epitope modulating transmission of bovine spongiform encephalopathy prions to transgenic mice. Proc Natl Acad Sci U S A 94, 14279–14284.[CrossRef]
    [Google Scholar]
  55. Scott, M. R., Will, R., Ironside, J., Nguyen, H.-O. B., Tremblay, P., DeArmond, S. J. & Prusiner, S. B. ( 1999; ). Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc Natl Acad Sci U S A 96, 15137–15142.[CrossRef]
    [Google Scholar]
  56. Scott, M. R., Peretz, D., Nguyen, H.-O. B., DeArmond, S. J. & Prusiner, S. B. ( 2005; ). Transmission barriers for bovine, ovine and human prions in transgenic mice. J Virol 79, 5259–5271.[CrossRef]
    [Google Scholar]
  57. 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 Pathol 39, 110–119.[CrossRef]
    [Google Scholar]
  58. Tamgüney, G., Giles, K., Bouzamondo-Bernstein, E., Bosque, P. J., Miller, M. W., Safar, J., DeArmond, S. J. & Prusiner, S. B. ( 2006; ). Transmission of elk and deer prions to transgenic mice. J Virol 80, 9104–9114.[CrossRef]
    [Google Scholar]
  59. Taraboulos, A., Jendroska, K., Serban, D., Yang, S.-L., DeArmond, S. J. & Prusiner, S. B. ( 1992; ). Regional mapping of prion proteins in brains. Proc Natl Acad Sci U S A 89, 7620–7624.[CrossRef]
    [Google Scholar]
  60. USDA ( 2008; ). Scrapie Program Monthly Report, April 2008. Washington, DC: United States Department of Agriculture.
  61. USGS National Wildlife Health Center ( 2007; ). Distribution of Chronic Wasting Disease in North America. Madison, WI: United States Geological Survey.
  62. Williams, E. S. ( 2005; ). Chronic wasting disease. Vet Pathol 42, 530–549.[CrossRef]
    [Google Scholar]
  63. Williams, E. S. & Young, S. ( 1980; ). Chronic wasting disease of captive mule deer: a spongiform encephalopathy. J Wildl Dis 16, 89–98.[CrossRef]
    [Google Scholar]
  64. Williams, E. S. & Young, S. ( 1992; ). Spongiform encephalopathies in Cervidae. Rev Sci Tech 11, 551–567.
    [Google Scholar]
  65. Wineland, N. E., Detwiler, L. A. & Salman, M. D. ( 1998; ). Epidemiologic analysis of reported scrapie in sheep in the United States: 1,117 cases (1947–1992). J Am Vet Med Assoc 212, 713–718.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.007500-0
Loading
/content/journal/jgv/10.1099/vir.0.007500-0
Loading

Data & Media loading...

Supplements

[ Single PDF file] (1.8 MB)

PDF

[ Single PDF file] (43 KB)

PDF

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