1887

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Volume 89, Issue 2

The elk codon 132 polymorphism controls cervid and scrapie prion propagation Free

Abstract

The elk prion protein gene () encodes either methionine (M) or leucine (L) at codon 132, the L132 allele apparently affording protection against chronic wasting disease (CWD). The corresponding human codon 129 polymorphism influences the host range of bovine spongiform encephalopathy (BSE) prions. To fully address the influence of this cervid polymorphism on CWD pathogenesis, we created transgenic (Tg) mice expressing cervid PrP with L at residue 132, referred to as CerPrP-L132, and compared the transmissibility of CWD prions from elk of defined genotypes, namely homozygous M/M or L/L or heterozygous M/L, in these Tg mice with previously described Tg mice expressing CerPrP-M132, referred to as Tg(CerPrP) mice. While Tg(CerPrP) mice were consistently susceptible to CWD prions from elk of all three genotypes, Tg(CerPrP-L132) mice uniformly failed to develop disease following challenge with CWD prions. In contrast, SSBP/1 sheep scrapie prions transmitted efficiently to both Tg(CerPrP) and Tg(CerPrP-L132) mice. Our findings suggest that the elk 132 polymorphism controls prion susceptibility at the level of prion strain selection and that cervid PrP L132 severely restricts propagation of CWD prions. We speculate that the L132 polymorphism results in less efficient conversion of CerPrP-L132 by CWD prions, an effect that is overcome by the SSBP/1 strain. Our studies show the accumulation of subclinical levels of CerPrP in aged asymptomatic CWD-inoculated Tg(CerPrP-L132) mice and also suggests the establishment of a latent infection state in apparently healthy elk expressing this seemingly protective allele.

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2008-02-01
2024-04-24
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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. 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]
  3. Baker H. E., Poulter M., Crow T. J., Frith C. D., Lofthouse R., Ridley R. M. 1991; Amino acid polymorphism in human prion protein and age at death in inherited prion disease. Lancet 337:1286
     [Google Scholar]
  4. Bessen R. A., Marsh R. F. 1994; Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy. J Virol 68:7859–7868
     [Google Scholar]
  5. Browning S. R., Mason G. L., Seward T., Green M., Eliason G. A., Mathiason C., Miller M. W., Williams E. S., Hoover E., Telling G. C. 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]
  6. Collinge J., Palmer M. S., Dryden A. J. 1991; Genetic predisposition to iatrogenic Creutzfeldt–Jakob disease. Lancet 337:1441–1442 [CrossRef]
     [Google Scholar]
  7. Collinge J., Palmer M. S., Sidle K. C., Hill A. F., Gowland I., Meads J., Asante E., Bradley R., Doey L. J., Lantos P. L. 1995; Unaltered susceptibility to BSE in transgenic mice expressing human prion protein. Nature 378:779–783 [CrossRef]
     [Google Scholar]
  8. Collinge J., Beck J., Campbell T., Estibeiro K., Will R. G. 1996a; Prion protein gene analysis in new variant cases of Creutzfeldt–Jakob disease. Lancet 348:56
     [Google Scholar]
  9. Collinge J., Sidle K. C. L., Meads J., Ironside J., Hill A. F. 1996b; Molecular analysis of prion strain variation and the aetiology of “new variant” CJD. Nature 383:685–690 [CrossRef]
     [Google Scholar]
  10. DeArmond S. J., Yang S.-L., Lee A., Bowler R., Taraboulos A., Groth D., Prusiner S. B. 1993; Three scrapie prion isolates exhibit different accumulation patterns of the prion protein scrapie isoform. Proc Natl Acad Sci U S A 90:6449–6453 [CrossRef]
     [Google Scholar]
  11. Dickinson A. G., Outram G. W., Taylor D. M., Foster J. D. 1989; Further evidence that scrapie agent has an independent genome. In Unconventional Virus Diseases of the Central Nervous System . pp 446–460Edited by Court L. A., Dormont D., Brown P., Kingsbury. Candé, France: L'Imprimerie Lefrancq et Cie;
  12. 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]
  13. Hecker R., Taraboulos A., Scott M., Pan K.-M., Torchia M., Jendroska K., DeArmond S. J., Prusiner S. B. 1992; Replication of distinct prion isolates is region specific in brains of transgenic mice and hamsters. Genes Dev 6:1213–1228 [CrossRef]
     [Google Scholar]
  14. Hill A. F., Desbruslais M., Joiner S., Sidle K. C. L., Gowland I., Collinge J., Doey L. J., Lantos P. 1997; The same prion strain causes vCJD and BSE. Nature 389:448–450 [CrossRef]
     [Google Scholar]
  15. Hunter N., Goldmann W., Marshall E., O'Neill G. 2000; Sheep and goats: natural and experimental TSEs and factors influencing incidence of disease. Arch Virol Suppl 16:181–188
     [Google Scholar]
  16. Johnson C., Johnson J., Vanderloo J. P., Keane D., Aiken J. M., McKenzie D. 2006; Prion protein polymorphisms in white-tailed deer influence susceptibility to chronic wasting disease. J Gen Virol 87:2109–2114 [CrossRef]
     [Google Scholar]
  17. 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]
  18. Kimura K. M., Yokoyama T., Haritani M., Narita M., Belleby P., Smith J., Spencer Y. I. 2002; In situ detection of cellular and abnormal isoforms of prion protein in brains of cattle with bovine spongiform encephalopathy and sheep with scrapie by use of a histoblot technique. J Vet Diagn Invest 14:255–257 [CrossRef]
     [Google Scholar]
  19. Kocisko D. A., Come J. H., Priola S. A., Chesebro B., Raymond G. J., Lansbury P. T. Jr, Caughey B. 1994; Cell-free formation of protease-resistant prion protein. Nature 370:471–474 [CrossRef]
     [Google Scholar]
  20. 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]
  21. Korth C., Stierli B., Streit P., Moser M., Schaller O., Fischer R., Schulz-Schaeffer W., Kretzschmar H., Raeber A. other authors 1997; Prion (PrPSc)-specific epitope defined by a monoclonal antibody. Nature 390:74–77 [CrossRef]
     [Google Scholar]
  22. Korth C., Kaneko K., Groth D., Heye N., Telling G., Mastrianni J., Parchi P., Gambetti P., Will R. other authors 2003; Abbreviated incubation times for human prions in mice expressing a chimeric mouse-human prion protein transgene. Proc Natl Acad Sci U S A 100:4784–4789 [CrossRef]
     [Google Scholar]
  23. LaFauci G., Carp R. I., Meeker H. C., Ye X., Kim J. I., Natelli M., Cedeno M., Petersen R. B., Kascsak R., Rubenstein R. 2006; Passage of chronic wasting disease prion into transgenic mice expressing Rocky Mountain elk ( Cervus elaphus nelsoni ) PrPC . J Gen Virol 87:3773–3780 [CrossRef]
     [Google Scholar]
  24. Lledo P.-M., Tremblay P., DeArmond S. J., Prusiner S. B., Nicoll R. A. 1996; Mice deficient for prion protein exhibit normal neuronal excitability and synaptic transmission in the hippocampus. Proc Natl Acad Sci U S A 93:2403–2407 [CrossRef]
     [Google Scholar]
  25. Mastrianni J. A., Nixon R., Layzer R., Telling G. C., Han D., DeArmond S. J., Prusiner S. B. 1999; Prion protein conformation in a patient with sporadic fatal insomnia. N Engl J Med 340:1630–1638 [CrossRef]
     [Google Scholar]
  26. 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 in transgenic mice expressing a naturally occurring allelic variant of deer prion protein. J Virol 81:4533–4539 [CrossRef]
     [Google Scholar]
  27. 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 alpha-helix. Nat Med 3:750–755 [CrossRef]
     [Google Scholar]
  28. Nonno R., Di Bari M. A., Cardone F., Vaccari G., Fazzi P., Dell'Omo G., Cartoni C., Ingrosso L., Boyle A. other authors 2006; Efficient transmission and characterization of Creutzfeldt–Jakob disease strains in bank voles. PLoS Pathog 2:e12 [CrossRef]
     [Google Scholar]
  29. O'Rourke K. I., Baszler T. V., Miller J. M., Spraker T. R., Sadler-Riggleman I., Knowles D. P. 1998; Monoclonal antibody F89/160.1.5 defines a conserved epitope on the ruminant prion protein. J Clin Microbiol 36:1750–1755
     [Google Scholar]
  30. 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]
  31. Palmer M. S., Dryden A. J., Hughes J. T., Collinge J. 1991; Homozygous prion protein genotype predisposes to sporadic Creutzfeldt–Jakob disease. Nature 352:340–342 [CrossRef]
     [Google Scholar]
  32. Peretz D., Williamson R. A., Legname G., Matsunaga Y., Vergara J., Burton D. R., 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]
  33. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144 [CrossRef]
     [Google Scholar]
  34. Prusiner S. B., Scott M., Foster D., Pan K.-M., Groth D., Mirenda C., Torchia M., Yang S.-L., Serban D. other authors 1990; Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63:673–686 [CrossRef]
     [Google Scholar]
  35. 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]
  36. 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]
  37. Schatzl H. M., Wopfner F., Gilch S., von Brunn A., Jager G. 1997; Is codon 129 of prion protein polymorphic in human beings but not in animals?. Lancet 349:1603–1604 [CrossRef]
     [Google Scholar]
  38. 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]
  39. 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]
  40. Scott M. R., Peretz D., Nguyen H. O., 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]
  41. 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 [CrossRef]
     [Google Scholar]
  42. 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]
  43. 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]
  44. Telling G. C., Scott M., Mastrianni J., Gabizon R., Torchia M., Cohen F. E., DeArmond S. J., Prusiner S. B. 1995; Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell 83:79–90 [CrossRef]
     [Google Scholar]
  45. Telling G. C., Parchi P., DeArmond S. J., Cortelli P., Montagna P., Gabizon R., Mastrianni J., Lugaresi E., Gambetti P., Prusiner S. B. 1996; Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity. Science 274:2079–2082 [CrossRef]
     [Google Scholar]
  46. 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]
  47. Wadsworth J. D. F., Hill A. F., Joiner S., Jackson G. S., Clarke A. R., Collinge J. 1999; Strain-specific prion-protein conformation determined by metal ions. Nat Cell Biol 1:55–59 [CrossRef]
     [Google Scholar]
  48. Wadsworth J. D., Asante E. A., Desbruslais M., Linehan J. M., Joiner S., Gowland I., Welch J., Stone L., Lloyd S. E. other authors 2004; Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science 306:1793–1796 [CrossRef]
     [Google Scholar]
  49. Westaway D., Goodman P. A., Mirenda C. A., McKinley M. P., Carlson G. A., Prusiner S. B. 1987; Distinct prion proteins in short and long scrapie incubation period mice. Cell 51:651–662 [CrossRef]
     [Google Scholar]
  50. Williams E. S. 2005; Chronic wasting disease. Vet Pathol 42:530–549 [CrossRef]
     [Google Scholar]
  51. Yokoyama T., Kimura K. M., Ushiki Y., Yamada S., Morooka A., Nakashiba T., Sassa T., Itohara S. 2001; In vivo conversion of cellular prion protein to pathogenic isoforms, as monitored by conformation-specific antibodies. J Biol Chem 276:11265–11271 [CrossRef]
     [Google Scholar]
  52. Zeidler M., Stewart G. E., Barraclough C. R., Bateman D. E., Bates D., Burn D. J., Colchester A. C., Durward W., Fletcher N. A. other authors 1997; New variant Creutzfeldt–Jakob disease: neurological features and diagnostic tests. Lancet 350:903–907 [CrossRef]
     [Google Scholar]
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The elk PRNP codon 132 polymorphism controls cervid and scrapie prion propagation
J. Gen. Virol. 89, 598 (2008); https://doi.org/10.1099/vir.0.83168-0
/content/journal/jgv/10.1099/vir.0.83168-0
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