1887

Abstract

The susceptibility of sheep to prion infection is linked to variation in the gene, which encodes the prion protein. Common polymorphisms occur at codons 136, 154 and 171. Sheep which are homozygous for the ARQ allele are the most susceptible to bovine spongiform encephalopathy (BSE). The effect of other polymorphisms on BSE susceptibility is unknown. We orally infected ARQ/ARQ Cheviot sheep with equal amounts of BSE brain homogenate and a range of incubation periods was observed. When we segregated sheep according to the amino acid (L or F) encoded at codon 141 of the gene, the shortest incubation period was observed in LL sheep, whilst incubation periods in FF and LF sheep were significantly longer. No statistically significant differences existed in the expression of total prion protein or the disease-associated isoform in BSE-infected sheep within each genotype subgroup. This suggested that the amino acid encoded at codon 141 probably affects incubation times through direct effects on protein misfolding rates.

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2012-12-01
2024-03-28
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References

  1. Andréoletti O., Morel N., Lacroux C., Rouillon V., Barc C., Tabouret G., Sarradin P., Berthon P., Bernardet P. other authors 2006; Bovine spongiform encephalopathy agent in spleen from an ARR/ARR orally exposed sheep. J Gen Virol 87:1043–1046[PubMed] [CrossRef]
    [Google Scholar]
  2. Barron R. M., Baybutt H., Tuzi N. L., McCormack J., King D., Moore R. C., Melton D. W., Manson J. C. 2005; Polymorphisms at codons 108 and 189 in murine PrP play distinct roles in the control of scrapie incubation time. J Gen Virol 86:859–868[PubMed] [CrossRef]
    [Google Scholar]
  3. Baylis M., Goldmann W. 2004; The genetics of scrapie in sheep and goats. Curr Mol Med 4:385–396[PubMed] [CrossRef]
    [Google Scholar]
  4. Benestad S. L., Sarradin P., Thu B., Schönheit J., Tranulis M. A., Bratberg B. 2003; Cases of scrapie with unusual features in Norway and designation of a new type, Nor98. Vet Rec 153:202–208[PubMed] [CrossRef]
    [Google Scholar]
  5. Bossers A., Schreuder B. E. C., Muileman I. H., Belt P. B. G. M., Smits M. A. 1996; PrP genotype contributes to determining survival times of sheep with natural scrapie. J Gen Virol 77:2669–2673[PubMed] [CrossRef]
    [Google Scholar]
  6. Bossers A., de Vries R., Smits M. A. 2000; Susceptibility of sheep for scrapie as assessed by in vitro conversion of nine naturally occurring variants of PrP. J Virol 74:1407–1414[PubMed] [CrossRef]
    [Google Scholar]
  7. Dawson M., Hoinville L. J., Hosie B. D., Hunter N. Scrapie Information Group 1998; Guidance on the use of PrP genotyping as an aid to the control of clinical scrapie. Vet Rec 142:623–625[PubMed]
    [Google Scholar]
  8. Detwiler L. A., Baylis M. 2003; The epidemiology of scrapie. Rev Sci Tech 22:121–143[PubMed]
    [Google Scholar]
  9. Foster J. D., Parnham D. W., Hunter N., Bruce M. 2001; Distribution of the prion protein in sheep terminally affected with BSE following experimental oral transmission. J Gen Virol 82:2319–2326[PubMed]
    [Google Scholar]
  10. Goldmann W. 2008; PrP genetics in ruminant transmissible spongiform encephalopathies. Vet Res 39:30[PubMed] [CrossRef]
    [Google Scholar]
  11. Goldmann W., Hunter N., Benson G., Foster J. D., Hope J. 1991; Different scrapie-associated fibril proteins (PrP) are encoded by lines of sheep selected for different alleles of the Sip gene. J Gen Virol 72:2411–2417 [CrossRef]
    [Google Scholar]
  12. Goldmann W., Hunter N., Smith G., Foster J., Hope J. 1994; PrP genotype and agent effects in scrapie: change of allelic interaction with different isolates of agent in sheep, a natural host of scrapie.. J Gen Virol 75:989–995 [CrossRef]
    [Google Scholar]
  13. Goldmann W., Houston F., Stewart P., Perucchini M., Foster J., Hunter N. 2006; Ovine prion protein variant A(136)R(154)L(168)Q(171) increases resistance to experimental challenge with bovine spongiform encephalopathy agent. J Gen Virol 87:3741–3745[PubMed] [CrossRef]
    [Google Scholar]
  14. Houston F., Goldmann W., Chong A., Jeffrey M., González L., Foster J., Parnham D., Hunter N. 2003; Prion diseases: BSE in sheep bred for resistance to infection. Nature 423:498–498[PubMed] [CrossRef]
    [Google Scholar]
  15. Houston F., McCutcheon S., Goldmann W., Chong A., Foster J., Sisó S., González L., Jeffrey M., Hunter N. 2008; Prion diseases are efficiently transmitted by blood transfusion in sheep. Blood 112:4739–4745[PubMed] [CrossRef]
    [Google Scholar]
  16. Hunter N., Goldmann W., Benson G., Foster J. D., Hope J. 1993; Swaledale sheep affected by natural scrapie differ significantly in Prp genotype frequencies from healthy sheep and those selected for reduced incidence of scrapie. J Gen Virol 74:1025–1031 [CrossRef]
    [Google Scholar]
  17. Jacobs J. G., Bossers A., Rezaei H., van Keulen L. J., McCutcheon S., Sklaviadis T., Lantier I., Berthon P., Lantier F. other authors 2011; Proteinase K-resistant material in ARR/VRQ sheep brain affected with classical scrapie is composed mainly of VRQ prion protein. J Virol 85:12537–12546[PubMed] [CrossRef]
    [Google Scholar]
  18. Kirby L., Goldmann W., Houston F., Gill A. C., Manson J. C. 2006; A novel, resistance-linked ovine PrP variant and its equivalent mouse variant modulate the in vitro cell-free conversion of rPrP to PrPres . J Gen Virol 87:3747–3751[PubMed] [CrossRef]
    [Google Scholar]
  19. Laegreid W. W., Clawson M. L., Heaton M. P., Green B. T., O’Rourke K. I., Knowles D. P. 2008; Scrapie resistance in ARQ sheep. J Virol 82:10318–10320[PubMed] [CrossRef]
    [Google Scholar]
  20. Manson J. C., Clarke A. R., McBride P. A., McConnell I., Hope J. 1994; PrP gene dosage determines the timing but not the final intensity or distribution of lesions in scrapie pathology. Neurodegeneration 3:331–340[PubMed]
    [Google Scholar]
  21. McCutcheon S., Hunter N., Houston F. 2005; Use of a new immunoassay to measure PrPSc levels in scrapie-infected sheep brains reveals PrP genotype-specific differences. J Immunol Methods 298:119–128[PubMed] [CrossRef]
    [Google Scholar]
  22. McCutcheon S., Alejo Blanco A. R., Houston E. F., de Wolf C., Tan B. C., Smith A., Groschup M. H., Hunter N., Hornsey V. S. other authors 2011; All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD. PLoS ONE 6:e23169[PubMed] [CrossRef]
    [Google Scholar]
  23. Morel N., Andréoletti O., Grassi J., Clément G. 2007; Absolute and relative quantification of sheep brain prion protein (PrP) allelic variants by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 21:4093–4100[PubMed] [CrossRef]
    [Google Scholar]
  24. Moum T., Olsaker I., Hopp P., Moldal T., Valheim M., Moum T., Benestad S. L. 2005; Polymorphisms at codons 141 and 154 in the ovine prion protein gene are associated with scrapie Nor98 cases. J Gen Virol 86:231–235[PubMed] [CrossRef]
    [Google Scholar]
  25. Saunders G. C., Lantier I., Cawthraw S., Berthon P., Moore S. J., Arnold M. E., Windl O., Simmons M. M., Andréoletti O. other authors 2009; Protective effect of the T112 PrP variant in sheep challenged with bovine spongiform encephalopathy. J Gen Virol 90:2569–2574[PubMed] [CrossRef]
    [Google Scholar]
  26. Tagliavini F., Prelli F., Porro M., Rossi G., Giaccone G., Farlow M. R., Dlouhy S. R., Ghetti B., Bugiani O., Frangione B. 1994; Amyloid fibrils in Gerstmann-Sträussler-Scheinker disease (Indiana and Swedish kindreds) express only PrP peptides encoded by the mutant allele. Cell 79:695–703[PubMed] [CrossRef]
    [Google Scholar]
  27. Vaccari G., D’Agostino C., Nonno R., Rosone F., Conte M., Di Bari M. A., Chiappini B., Esposito E., De Grossi L. other authors 2007; Prion protein alleles showing a protective effect on the susceptibility of sheep to scrapie and bovine spongiform encephalopathy. J Virol 81:7306–7309[PubMed] [CrossRef]
    [Google Scholar]
  28. Vaccari G., Scavia G., Sala M., Cosseddu G., Chiappini B., Conte M., Esposito E., Lorenzetti R., Perfetti G. other authors 2009; Protective effect of the AT137RQ and ARQK176 PrP allele against classical scrapie in Sarda breed sheep. Vet Res 40:19[PubMed] [CrossRef]
    [Google Scholar]
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