1887

Abstract

In mammals, susceptibility to prion infection is primarily modulated by the host’s cellular prion protein (PrP) sequence. In the sheep scrapie model, a graded scale of susceptibility has been established both and based on PrP amino acids 136, 154 and 171, leading to global breeding programmes to reduce the prevalence of scrapie in sheep. Chronic wasting disease (CWD) resistance in cervids is often characterized as decreased prevalence and/or protracted disease progression in individuals with specific alleles; at present, no PrP allele conferring absolute resistance in cervids has been identified. To model the susceptibility of various naturally occurring and hypothetical cervid PrP alleles , we compared the amplification rates and amyloid extension efficiencies of eight distinct CWD isolates in recombinant cervid PrP substrates using real-time quaking-induced conversion. We hypothesized that the conversion characteristics of these isolates in cervid substrates would correlate to susceptibility – permitting susceptibility prediction for the rare alleles found in nature. We also predicted that hypothetical alleles with multiple resistance-associated codons would be more resistant to conversion than natural alleles with a single resistant codon. Our studies demonstrate that conversion metrics align with susceptibility, and that alleles with multiple amino acid substitutions, each influencing resistance independently, do not necessarily contribute additively to conversion resistance. Importantly, we found that the naturally occurring whitetail deer QGAK substrate exhibited the slowest amplification rate among those evaluated, suggesting that further investigation of this allele and its resistance is warranted.

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2017-11-01
2024-04-19
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References

  1. Williams ES, Young S. Chronic wasting disease of captive mule deer: a spongiform encephalopathy. J Wildl Dis 1980; 16:89–98 [View Article][PubMed]
    [Google Scholar]
  2. Heisey DM, Mickelsen NA, Schneider JR, Johnson CJ, Johnson CJ et al. Chronic wasting disease (CWD) susceptibility of several North American rodents that are sympatric with cervid CWD epidemics. J Virol 2010; 84:210–215 [View Article][PubMed]
    [Google Scholar]
  3. Nalls AV, Mcnulty E, Powers J, Seelig DM, Hoover C et al. Mother to offspring transmission of chronic wasting disease in reeves' muntjac deer. PLoS One 2013; 8:e71844 [View Article][PubMed]
    [Google Scholar]
  4. Marsh RF, Kincaid AE, Bessen RA, Bartz JC. Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiri sciureus). J Virol 2005; 79:13794–13796 [View Article][PubMed]
    [Google Scholar]
  5. Race B, Meade-White KD, Phillips K, Striebel J, Race R et al. Chronic wasting disease agents in nonhuman primates. Emerg Infect Dis 2014; 20:833–837 [View Article][PubMed]
    [Google Scholar]
  6. Haley NJ, Hoover EA. Chronic wasting disease of cervids: current knowledge and future perspectives. Annu Rev Anim Biosci 2015; 3:305–325 [View Article][PubMed]
    [Google Scholar]
  7. 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; 47:88 [View Article][PubMed]
    [Google Scholar]
  8. Wolfe LL, Fox KA, Miller MW. "Atypical" chronic wasting disease in PRNP genotype 225FF mule deer. J Wildl Dis 2014; 50:660–665 [View Article][PubMed]
    [Google Scholar]
  9. Johnson C, Johnson J, Vanderloo JP, Keane D, Aiken JM et al. Prion protein polymorphisms in white-tailed deer influence susceptibility to chronic wasting disease. J Gen Virol 2006; 87:2109–2114 [View Article][PubMed]
    [Google Scholar]
  10. Kelly AC, Mateus-Pinilla NE, Diffendorfer J, Jewell E, Ruiz MO et al. Prion sequence polymorphisms and chronic wasting disease resistance in Illinois white-tailed deer (Odocoileus virginianus). Prion 2008; 2:28–36 [View Article][PubMed]
    [Google Scholar]
  11. Robinson SJ, Samuel MD, O'Rourke KI, Johnson CJ. The role of genetics in chronic wasting disease of North American cervids. Prion 2012; 6:153–162 [View Article][PubMed]
    [Google Scholar]
  12. Haley NJ, Siepker C, Hoon-Hanks LL, Mitchell G, Walter WD et al. Seeded amplification of chronic wasting disease prions in nasal brushings and recto-anal mucosa-associated lymphoid tissues from elk by real-time quaking-induced conversion. J Clin Microbiol 2016; 54:1117–1126 [View Article][PubMed]
    [Google Scholar]
  13. Haley NJ, Siepker C, Walter WD, Thomsen BV, Greenlee JJ et al. Antemortem detection of chronic wasting disease prions in nasal brush collections and rectal biopsy specimens from white-tailed deer by real-time quaking-induced conversion. J Clin Microbiol 2016; 54:1108–1116 [View Article][PubMed]
    [Google Scholar]
  14. O'Rourke KI, Spraker TR, Hamburg LK, Besser TE, Brayton KA et al. 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 2004; 85:1339–1346 [View Article][PubMed]
    [Google Scholar]
  15. O'Rourke KI, Spraker TR, Zhuang D, Greenlee JJ, Gidlewski TE et al. Elk with a long incubation prion disease phenotype have a unique PrPd profile. Neuroreport 2007; 18:1935–1938 [View Article][PubMed]
    [Google Scholar]
  16. Lloyd SE, Mead S, Collinge J. Genetics of prion diseases. Curr Opin Genet Dev 2013; 23:345–351 [View Article][PubMed]
    [Google Scholar]
  17. 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 [View Article][PubMed]
    [Google Scholar]
  18. O'Rourke KI, Besser TE, Miller MW, Cline TF, Spraker TR et al. PrP genotypes of captive and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease. J Gen Virol 1999; 80:2765–2679 [View Article][PubMed]
    [Google Scholar]
  19. Perucchini M, Griffin K, Miller MW, Goldmann W. PrP genotypes of free-ranging wapiti (Cervus elaphus nelsoni) with chronic wasting disease. J Gen Virol 2008; 89:1324–1328 [View Article][PubMed]
    [Google Scholar]
  20. Geremia C, Hoeting JA, Wolfe LL, Galloway NL, Antolin MF et al. Age and repeated biopsy influence antemortem PRPCWD testing in mule deer (Odocoileus hemionus) in Colorado, USA. J Wildl Dis 2015; 51:801–810 [View Article][PubMed]
    [Google Scholar]
  21. Jewell JE, Conner MM, Wolfe LL, Miller MW, Williams ES. Low frequency of PrP genotype 225SF among free-ranging mule deer (Odocoileus hemionus) with chronic wasting disease. J Gen Virol 2005; 86:2127–2134 [View Article][PubMed]
    [Google Scholar]
  22. Hamir AN, Greenlee JJ, Nicholson EM, Kunkle RA, Richt JA et al. Experimental transmission of chronic wasting disease (CWD) from elk and white-tailed deer to fallow deer by intracerebral route: final report. Can J Vet Res 2011; 75:152–156[PubMed]
    [Google Scholar]
  23. Mitchell GB, Sigurdson CJ, O'Rourke KI, Algire J, Harrington NP et al. Experimental oral transmission of chronic wasting disease to reindeer (Rangifer tarandus tarandus). PLoS One 2012; 7:e39055 [View Article][PubMed]
    [Google Scholar]
  24. Moore SJ, Kunkle R, Greenlee MH, Nicholson E, Richt J et al. Horizontal transmission of chronic wasting disease in reindeer. Emerg Infect Dis 2016; 22:2142–2145 [View Article][PubMed]
    [Google Scholar]
  25. Rhyan JC, Miller MW, Spraker TR, Mccollum M, Nol P et al. Failure of fallow deer (Dama dama) to develop chronic wasting disease when exposed to a contaminated environment and infected mule deer (Odocoileus hemionus). J Wildl Dis 2011; 47:739–744 [View Article][PubMed]
    [Google Scholar]
  26. Johnson RT. Prion diseases. Lancet Neurol 2005; 4:635–642 [View Article]
    [Google Scholar]
  27. Kurt TD, Perrott MR, Wilusz CJ, Wilusz J, Supattapone S et al. Efficient in vitro amplification of chronic wasting disease PrPRES . J Virol 2007; 81:9605–9608 [View Article][PubMed]
    [Google Scholar]
  28. Saborio GP, Permanne B, Soto C. Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 2001; 411:810–813 [View Article][PubMed]
    [Google Scholar]
  29. Haley NJ, Mathiason CK, Carver S, Telling GC, Zabel MD et al. Sensitivity of protein misfolding cyclic amplification versus immunohistochemistry in ante-mortem detection of chronic wasting disease. J Gen Virol 2012; 93:1141–1150 [View Article][PubMed]
    [Google Scholar]
  30. Saá P, Castilla J, Soto C. Ultra-efficient replication of infectious prions by automated protein misfolding cyclic amplification. J Biol Chem 2006; 281:35245–35252 [View Article][PubMed]
    [Google Scholar]
  31. Atarashi R, Moore RA, Sim VL, Hughson AG, Dorward DW et al. Ultrasensitive detection of scrapie prion protein using seeded conversion of recombinant prion protein. Nat Methods 2007; 4:645–650 [View Article][PubMed]
    [Google Scholar]
  32. Orrú CD, Favole A, Corona C, Mazza M, Manca M et al. Detection and discrimination of classical and atypical L-type bovine spongiform encephalopathy by real-time quaking-induced conversion. J Clin Microbiol 2015; 53:1115–1120 [View Article][PubMed]
    [Google Scholar]
  33. Davenport KA, Henderson DM, Bian J, Telling GC, Mathiason CK et al. Insights into chronic wasting disease and bovine spongiform encephalopathy species barriers by use of real-time conversion. J Virol 2015; 89:9524–9531 [View Article][PubMed]
    [Google Scholar]
  34. Arnold M, Ortiz-Pelaez A. The evolution of the prevalence of classical scrapie in sheep in Great Britain using surveillance data between 2005 and 2012. Prev Vet Med 2014; 117:242–250 [View Article]
    [Google Scholar]
  35. Hagenaars TJ, Melchior MB, Bossers A, Davidse A, Engel B et al. Scrapie prevalence in sheep of susceptible genotype is declining in a population subject to breeding for resistance. BMC Vet Res 2010; 6:25 [View Article][PubMed]
    [Google Scholar]
  36. Sutton D. (editor). USDA-APHIS Scrapie Program Update and Scrapie Surveillance Projects One Hundred and Nineteenth Annual Meeting of the United States Animal Health Association Providence, RI: 2015
    [Google Scholar]
  37. Bradley R, Wilesmith JW. Epidemiology and control of bovine spongiform encephalopathy (BSE). Br Med Bull 1993; 49:932–959 [View Article][PubMed]
    [Google Scholar]
  38. Stokstad E. Norway plans to exterminate a large reindeer herd to stop a fatal infectious brain disease. Science 2017 [View Article]
    [Google Scholar]
  39. Baylis M, Goldmann W. The genetics of scrapie in sheep and goats. Curr Mol Med 2004; 4:385–396 [View Article][PubMed]
    [Google Scholar]
  40. Francois D, Elsen JM, Barillet F, Lajous D, Eychenne F et al. Breeding sheep for scrapie resistance. In Breeding Programmes for Improving the Quality and Safety of Products New Traits, Tools, Rules and Organization [Internet] Zaragoza: CIHEAM; 2003 pp. 29–35 http://om.iamm.fr/om/pdf/a55/03600060.pdf
    [Google Scholar]
  41. Thorne L, Holder T, Ramsay A, Edwards J, Taema MM et al. In vitro amplification of ovine prions from scrapie-infected sheep from Great Britain reveals distinct patterns of propagation. BMC Vet Res 2012; 8:223 [View Article][PubMed]
    [Google Scholar]
  42. Bucalossi C, Cosseddu G, D'Agostino C, di Bari MA, Chiappini B et al. Assessment of the genetic susceptibility of sheep to scrapie by protein misfolding cyclic amplification and comparison with experimental scrapie transmission studies. J Virol 2011; 85:8386–8392 [View Article][PubMed]
    [Google Scholar]
  43. 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 [View Article][PubMed]
    [Google Scholar]
  44. Raymond GJ, Raymond LD, Meade-White KD, Hughson AG, Favara C et al. Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains. J Virol 2007; 81:4305–4314 [View Article][PubMed]
    [Google Scholar]
  45. Perrott MR, Sigurdson CJ, Mason GL, Hoover EA. Evidence for distinct chronic wasting disease (CWD) strains in experimental CWD in ferrets. J Gen Virol 2012; 93:212–221 [View Article][PubMed]
    [Google Scholar]
  46. 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 [View Article][PubMed]
    [Google Scholar]
  47. Wilson GA, Nakada SM, Bollinger TK, Pybus MJ, Merrill EH et al. Polymorphisms at the PRNP gene influence susceptibility to chronic wasting disease in two species of deer (Odocoileus Spp.) in western Canada. J Toxicol Environ Health A 2009; 72:1025–1029 [View Article][PubMed]
    [Google Scholar]
  48. Keane DP, Barr DJ, Bochsler PN, Hall SM, Gidlewski T et al. Chronic wasting disease in a Wisconsin white-tailed deer farm. J Vet Diagn Invest 2008; 20:698–703 [View Article][PubMed]
    [Google Scholar]
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