1887

Abstract

Chronic wasting disease (CWD) is a prion disease that affects free-ranging and captive cervids, including mule deer, white-tailed deer, Rocky Mountain elk and moose. CWD-infected cervids have been reported in 14 USA states, two Canadian provinces and in South Korea. The possibility of a zoonotic transmission of CWD prions via diet is of particular concern in North America where hunting of cervids is a popular sport. To investigate the potential public health risks posed by CWD prions, we have investigated whether intracerebral inoculation of brain and spinal cord from CWD-infected mule deer transmits prion infection to transgenic mice overexpressing human prion protein with methionine or valine at polymorphic residue 129. These transgenic mice have been utilized in extensive transmission studies of human and animal prion disease and are susceptible to BSE and vCJD prions, allowing comparison with CWD. Here, we show that these mice proved entirely resistant to infection with mule deer CWD prions arguing that the transmission barrier associated with this prion strain/host combination is greater than that observed with classical BSE prions. However, it is possible that CWD may be caused by multiple prion strains. Further studies will be required to evaluate the transmission properties of distinct cervid prion strains as they are characterized.

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2010-10-01
2024-04-19
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References

  1. Anderson, C. A., Bosque, P., Filley, C. M., Arciniegas, D. B., Kleinschmidt-Demasters, B. K., Pape, W. J. & Tyler, K. L.(2007). Colorado surveillance program for chronic wasting disease transmission to humans: lessons from 2 highly suspicious but negative cases. Arch Neurol 64, 439–441.[CrossRef] [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.[CrossRef] [Google Scholar]
  3. Angers, R. C., Kang, H. E., Napier, D., Browning, S., Seward, T., Mathiason, C., Balachandran, A., McKenzie, D., Castilla, J. & other authors(2010). Prion strain mutation determined by prion protein conformational compatibility and primary structure. Science 328, 1154–1158.[CrossRef] [Google Scholar]
  4. Asante, E. A., Linehan, J. M., Desbruslais, M., Joiner, S., Gowland, I., Wood, A. L., Welch, J., Hill, A. F., Lloyd, S. E. & other authors(2002). BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J 21, 6358–6366.[CrossRef] [Google Scholar]
  5. Asante, E. A., Linehan, J. M., Gowland, I., Joiner, S., Fox, K., Cooper, S., Osiguwa, O., Gorry, M., Welch, J. & other authors(2006). Dissociation of pathological and molecular phenotype of variant Creutzfeldt–Jakob disease in transgenic human prion protein 129 heterozygous mice. Proc Natl Acad Sci U S A 103, 10759–10764.[CrossRef] [Google Scholar]
  6. 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]
  7. Belay, E. D.(2004). Chronic wasting disease and potential transmission to humans. Emerg Infect Dis 10, 977–984.[CrossRef] [Google Scholar]
  8. Belay, E. D., Gambetti, P., Schonberger, L. B., Parchi, P., Lyon, D. R., Capellari, S., McQuiston, J. H., Bradley, K., Dowdle, G. & other authors(2001). Creutzfeldt–Jakob disease in unusually young patients who consumed venison. Arch Neurol 58, 1673–1678.[CrossRef] [Google Scholar]
  9. Beringue, V., Vilotte, J. L. & Laude, H.(2008). Prion agents diversity and species barrier. Vet Res 39, 47.[CrossRef] [Google Scholar]
  10. Browning, S. R., Mason, G. L., Seward, T., Green, M., Eliason, G. A., Mathiason, C., Miller, M. W., Williams, E. S., Hoover, E. & other authors(2004). Transmission of prions from mule deer and elk with chronic wasting disease to transgenic mice expressing cervid PrP. J Virol 78, 13345–13350.[CrossRef] [Google Scholar]
  11. Bruce, M. E., Will, R. G., Ironside, J. W., McConnell, I., Drummond, D., Suttie, A., McCardle, L., Chree, A., Hope, J. & other authors(1997). Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389, 498–501.[CrossRef] [Google Scholar]
  12. Castilla, J., Gonzalez-Romero, D., Saa, P., Morales, R., De Castro, J. & Soto, C.(2008). Crossing the species barrier by PrPSc replication in vitro generates unique infectious prions. Cell 134, 757–768.[CrossRef] [Google Scholar]
  13. Collinge, J.(1999). Variant Creutzfeldt–Jakob disease. Lancet 354, 317–323.[CrossRef] [Google Scholar]
  14. Collinge, J.(2010). Prion strain mutation and selection. Science 328, 1111–1112.[CrossRef] [Google Scholar]
  15. Collinge, J. & Clarke, A. R.(2007). A general model of prion strains and their pathogenicity. Science 318, 930–936.[CrossRef] [Google Scholar]
  16. Collinge, J., Palmer, M. S., Sidle, K. C. L., Gowland, I., Medori, R., Ironside, J. & Lantos, P. L.(1995a). Transmission of fatal familial insomnia to laboratory animals. Lancet 346, 569–570.[CrossRef] [Google Scholar]
  17. Collinge, J., Palmer, M. S., Sidle, K. C. L., Hill, A. F., Gowland, I., Meads, J., Asante, E., Bradley, R., Doey, L. J. & other authors(1995b). Unaltered susceptibility to BSE in transgenic mice expressing human prion protein. Nature 378, 779–783.[CrossRef] [Google Scholar]
  18. Collinge, J., Sidle, K. C. L., Meads, J., Ironside, J. & Hill, A. F.(1996). Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 383, 685–690.[CrossRef] [Google Scholar]
  19. Collinge, J., Whitfield, J., McKintosh, E., Beck, J., Mead, S., Thomas, D. J. & Alpers, M. P.(2006). Kuru in the 21st century – an acquired human prion disease with very long incubation periods. Lancet 367, 2068–2074.[CrossRef] [Google Scholar]
  20. Collinge, J., Whitfield, J., McKintosh, E., Frosh, A., Mead, S., Hill, A. F., Brandner, S., Thomas, D. & Alpers, M. P.(2008). A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New Guinea. Philos Trans R Soc Lond B Biol Sci 363, 3725–3739.[CrossRef] [Google Scholar]
  21. Fox, K. A., Jewell, J. E., Williams, E. S. & Miller, M. W.(2006). Patterns of PrPCWD accumulation during the course of chronic wasting disease infection in orally inoculated mule deer (Odocoileus hemionus). J Gen Virol 87, 3451–3461.[CrossRef] [Google Scholar]
  22. 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]
  23. Guiroy, D. C., Williams, E. S., Song, K.-J., Yanagihara, R. & Gajdusek, D. C.(1993). Fibrils in brains of Rocky Mountain elk with chronic wasting disease contain scrapie amyloid. Acta Neuropathol 86, 77–80.[CrossRef] [Google Scholar]
  24. Haley, N. J., Seelig, D. M., Zabel, M. D., Telling, G. C. & Hoover, E. A.(2009). Detection of CWD prions in urine and saliva of deer by transgenic mouse bioassay. PLoS ONE 4, e4848.[CrossRef] [Google Scholar]
  25. Hamir, A. N., Gidlewski, T., Spraker, T. R., Miller, J. M., Creekmore, L., Crocheck, M., Cline, T. & O'Rourke, K. I.(2006). Preliminary observations of genetic susceptibility of elk (Cervus elaphus nelsoni) to chronic wasting disease by experimental oral inoculation. J Vet Diagn Invest 18, 110–114.[CrossRef] [Google Scholar]
  26. 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.[CrossRef] [Google Scholar]
  27. Hill, A. F., Desbruslais, M., Joiner, S., Sidle, K. C. L., Gowland, I. & Collinge, J.(1997). The same prion strain causes vCJD and BSE. Nature 389, 448–450.[CrossRef] [Google Scholar]
  28. Jennelle, C. S., Samuel, M. D., Nolden, C. A., Keane, D. P., Barr, D. J., Johnson, C., Vanderloo, J. P., Aiken, J. M., Hamir, A. N. & other authors(2009). Surveillance for transmissible spongiform encephalopathy in scavengers of white-tailed deer carcasses in the chronic wasting disease area of Wisconsin. J Toxicol Environ Health A 72, 1018–1024.[CrossRef] [Google Scholar]
  29. Kascsak, R. J., Rubenstein, R., Merz, P. A., Tonna DeMasi, M., Fersko, R., Carp, R. I., Wisniewski, H. M. & Diringer, H.(1987). Mouse polyclonal and monoclonal antibody to scrapie-associated fibril proteins. J Virol 61, 3688–3693. [Google Scholar]
  30. 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]
  31. 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, 7944–7949.[CrossRef] [Google Scholar]
  32. Kong, Q., Zheng, M., Casalone, C., Qing, L., Huang, S., Chakraborty, B., Wang, P., Chen, F., Cali, I. & other authors(2008). Evaluation of the human transmission risk of an atypical bovine spongiform encephalopathy prion strain. J Virol 82, 3697–3701.[CrossRef] [Google Scholar]
  33. 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]
  34. Lloyd, S. E., Linehan, J. M., Desbruslais, M., Joiner, S., Buckell, J., Brandner, S., Wadsworth, J. D. & Collinge, J.(2004). Characterization of two distinct prion strains derived from bovine spongiform encephalopathy transmissions to inbred mice. J Gen Virol 85, 2471–2478.[CrossRef] [Google Scholar]
  35. Lloyd, S. E., Maytham, E. G., Pota, H., Grizenkova, J., Molou, E., Uphill, J., Hummerich, H., Whitfield, J., Alpers, M. P. & other authors(2009). HECTD2 is associated with susceptibility to mouse and human prion disease. PLoS Genet 5, e1000383.[CrossRef] [Google Scholar]
  36. 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.[CrossRef] [Google Scholar]
  37. 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]
  38. 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.[CrossRef] [Google Scholar]
  39. 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]
  40. Mead, S., Poulter, M., Uphill, J., Beck, J., Whitfield, J., Webb, T. E., Campbell, T., Adamson, G., Deriziotis, P. & other authors(2009). Genetic risk factors for variant Creutzfeldt–Jakob disease: a genome-wide association study. Lancet Neurol 8, 57–66.[CrossRef] [Google Scholar]
  41. Meade-White, K., Race, B., Trifilo, M., Bossers, A., Favara, C., LaCasse, R., Miller, M., Williams, E., Oldstone, M. & other authors(2007). Resistance to chronic wasting disease (CWD) in transgenic mice expressing a naturally occurring allelic variant of deer prion protein. J Virol 81, 4533–4539.[CrossRef] [Google Scholar]
  42. Nichols, T. A., Pulford, B., Wyckoff, A. C., Meyerett, C., Michel, B., Gertig, K., Hoover, E. A., Jewell, J. E., Telling, G. C. & other authors(2009). Detection of protease-resistant cervid prion protein in water from a CWD-endemic area. Prion 3, 171–183.[CrossRef] [Google Scholar]
  43. O'Rourke, K. I., Spraker, T. R., Hamburg, L. K., Besser, T. E., Brayton, K. A. & Knowles, D. P.(2004). Polymorphisms in the prion precursor functional gene but not the pseudogene are associated with susceptibility to chronic wasting disease in white-tailed deer. J Gen Virol 85, 1339–1346.[CrossRef] [Google Scholar]
  44. Prusiner, S. B.(1998). Prions. Proc Natl Acad Sci U S A 95, 13363–13383.[CrossRef] [Google Scholar]
  45. Race, R. E., Raines, A., Baron, T. G., Miller, M. W., Jenny, A. & Williams, E. S.(2002). Comparison of abnormal prion protein glycoform patterns from transmissible spongiform encephalopathy agent-infected deer, elk, sheep, and cattle. J Virol 76, 12365–12368.[CrossRef] [Google Scholar]
  46. Race, B., Meade-White, K., Race, R. & Chesebro, B.(2009a). Prion infectivity in fat of deer with chronic wasting disease. J Virol 83, 9608–9610.[CrossRef] [Google Scholar]
  47. Race, B., Meade-White, K. D., Miller, M. W., Barbian, K. D., Rubenstein, R., LaFauci, G., Cervenakova, L., Favara, C., Gardner, D. & other authors(2009b). Susceptibilities of nonhuman primates to chronic wasting disease. Emerg Infect Dis 15, 1366–1376.[CrossRef] [Google Scholar]
  48. 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. & other authors(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]
  49. 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. & other authors(2007). Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains. J Virol 81, 4305–4314.[CrossRef] [Google Scholar]
  50. 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]
  51. Sigurdson, C. J.(2008). A prion disease of cervids: chronic wasting disease. Vet Res 39, 41.[CrossRef] [Google Scholar]
  52. Sigurdson, C. J. & Aguzzi, A.(2007). Chronic wasting disease. Biochim Biophys Acta 1772, 610–618.[CrossRef] [Google Scholar]
  53. 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. & other authors(2008). Experimental chronic wasting disease (CWD) in the ferret. J Comp Pathol 138, 189–196.[CrossRef] [Google Scholar]
  54. Tamguney, 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]
  55. Tamguney, 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.[CrossRef] [Google Scholar]
  56. Trifilo, M. J., Ying, G., Teng, C. & Oldstone, M. B.(2007). Chronic wasting disease of deer and elk in transgenic mice: oral transmission and pathobiology. Virology 365, 136–143.[CrossRef] [Google Scholar]
  57. Wadsworth, J. D. & Collinge, J.(2007). Update on human prion disease. Biochim Biophys Acta 1772, 598–609.[CrossRef] [Google Scholar]
  58. 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 CJD using a highly sensitive immuno-blotting assay. Lancet 358, 171–180.[CrossRef] [Google Scholar]
  59. Wadsworth, J. D., Asante, E., Desbruslais, M., Linehan, J., Joiner, S., Gowland, I., Welch, J., Stone, L., Lloyd, S. & other authors(2004). Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science 306, 1793–1796.[CrossRef] [Google Scholar]
  60. Wadsworth, J. D., Joiner, S., Fox, K., Linehan, J., Desbruslais, M., Brandner, S., Asante, E. & Collinge, J.(2007). Prion infectivity in variant Creutzfeldt–Jakob disease rectum. Gut 56, 90–94.[CrossRef] [Google Scholar]
  61. Wadsworth, J. D., Joiner, S., Linehan, J. M., Desbruslais, M., Fox, K., Cooper, S., Cronier, S., Asante, E. A., Mead, S. & other authors(2008a). Kuru prions and sporadic Creutzfeldt–Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice. Proc Natl Acad Sci U S A 105, 3885–3890.[CrossRef] [Google Scholar]
  62. Wadsworth, J. D., Powell, C., Beck, J. A., Joiner, S., Linehan, J. M., Brandner, S., Mead, S. & Collinge, J.(2008b). Molecular diagnosis of human prion disease. Methods Mol Biol 459, 197–227. [Google Scholar]
  63. Williams, E. S.(2005). Chronic wasting disease. Vet Pathol 42, 530–549.[CrossRef] [Google Scholar]
  64. 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]
  65. Williams, E. S. & Young, S.(1982). Spongiform encephalopathy of Rocky Mountain elk. J Wildl Dis 18, 465–471.[CrossRef] [Google Scholar]
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