1887

Abstract

Sheep with an ARQ/ARQ genotype at codon positions 136/154/171 are highly susceptible to experimental infection with bovine spongiform encephalopathy (BSE). However, a number of sheep challenged orally or intracerebrally with BSE were clinically asymptomatic and found to survive or were diagnosed as BSE-negative when culled. Sequencing of the full gene open reading frame of BSE-susceptible and -resistant sheep indicated that, in the majority of Suffolk sheep, resistance was associated with an M112T variant (TARQ allele). A high proportion (47 of 49; 96 %) of BSE-challenged wild-type (MARQ/MARQ) Suffolk sheep were BSE-infected, whereas none of the 20 sheep with at least one TARQ allele succumbed to BSE. Thirteen TARQ-carrying sheep challenged with BSE are still alive and some have survival periods equivalent to, or greater than, reported incubation periods of BSE in ARR/ARR and VRQ/VRQ sheep.

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2009-10-01
2020-01-17
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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.[CrossRef]
    [Google Scholar]
  2. Babar, M. E., Farid, A., Benkel, B. F., Ahmad, J., Nadeem, A. & Imran, M. ( 2009; ). Frequencies of PrP genotypes and their implication for breeding against scrapie susceptibility in nine Pakistani sheep breeds. Mol Biol Rep 36, 561–565.[CrossRef]
    [Google Scholar]
  3. Baylis, M. ( 2002; ). The BSE-susceptible proportion of UK sheep. Vet Rec 151, 481–482.[CrossRef]
    [Google Scholar]
  4. Bellworthy, S. J., Hawkins, S. A., Green, R. B., Blamire, I., Dexter, G., Dexter, I., Lockey, R., Jeffrey, M., Ryder, S. & other authors ( 2005a; ). Tissue distribution of bovine spongiform encephalopathy infectivity in Romney sheep up to the onset of clinical disease after oral challenge. Vet Rec 156, 197–202.[CrossRef]
    [Google Scholar]
  5. Bellworthy, S. J., Dexter, G., Stack, M., Chaplin, M., Hawkins, S. A., Simmons, M. M., Jeffrey, M., Martin, S., Gonzalez, L. & other authors ( 2005b; ). Natural transmission of BSE between sheep within an experimental flock. Vet Rec 157, 206 [CrossRef]
    [Google Scholar]
  6. Bellworthy, S. J., Dexter, G., Stack, M., Chaplin, M., Hawkins, S. A., Simmons, M. M., Jeffrey, M., Martin, S., Gonzalez, L. & other authors ( 2008; ). Oral transmission of BSE to VRQ/VRQ sheep in an experimental flock. Vet Rec 162, 130–131.
    [Google Scholar]
  7. 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.[CrossRef]
    [Google Scholar]
  8. 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]
  9. Collinge, J., Sidle, K. C., 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]
  10. Eloit, M., Adjou, K., Coulpier, M., Fontaine, J. J., Hamel, R., Lilin, T., Messiaen, S., Andréoletti, O., Baron, T. & other authors ( 2005; ). BSE agent signatures in a goat. Vet Rec 156, 523–524.
    [Google Scholar]
  11. Ferguson, N. M., Ghani, A. C., Donnelly, C. A., Hagenaars, T. J. & Anderson, R. M. ( 2002; ). Estimating the human health risk from possible BSE infection of the British sheep flock. Nature 415, 420–424.[CrossRef]
    [Google Scholar]
  12. Foster, J. D., Parnham, D. W., Hunter, N. & Bruce, M. ( 2001a; ). Distribution of the prion protein in sheep terminally affected with BSE following experimental oral transmission. J Gen Virol 82, 2319–2326.
    [Google Scholar]
  13. Foster, J. D., Parnham, D., Chong, A., Goldmann, W. & Hunter, N. ( 2001b; ). Clinical signs, histopathology and genetics of experimental transmission of BSE and natural scrapie to sheep and goats. Vet Rec 148, 165–171.[CrossRef]
    [Google Scholar]
  14. Fryer, H. R., Baylis, M., Sivam, K. & McLean, A. R. ( 2007; ). Quantifying the risk from ovine BSE and the impact of control strategies. Proc Biol Sci 274, 1497–1503.[CrossRef]
    [Google Scholar]
  15. Gavier-Widén, D., Stack, M. J., Baron, T., Balachandran, A. & Simmons, M. ( 2005; ). Diagnosis of transmissible spongiform encephalopathies in animals: a review. J Vet Diagn Invest 17, 509–527.[CrossRef]
    [Google Scholar]
  16. 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]
  17. Goldmann, W., Baylis, M., Chihota, C., Stevenson, E. & Hunter, N. ( 2005; ). Frequencies of PrP gene haplotypes in British sheep flocks and the implications for breeding programmes. J Appl Microbiol 98, 1294–1302.[CrossRef]
    [Google Scholar]
  18. Goldmann, W., Houston, F., Stewart, P., Perucchini, M., Foster, J. & Hunter, N. ( 2006; ). Ovine prion protein variant A136R154L168Q171 increases resistance to experimental challenge with bovine spongiform encephalopathy agent. J Gen Virol 87, 3741–3745.[CrossRef]
    [Google Scholar]
  19. Gombojav, A., Ishiguro, N., Horiuchi, M. & Shinagawa, M. ( 2004; ). Unique amino acid polymorphisms of PrP genes in Mongolian sheep breeds. J Vet Med Sci 66, 1293–1295.[CrossRef]
    [Google Scholar]
  20. Heaton, M. P., Leymaster, K. A., Freking, B. A., Hawk, D. A., Smith, T. P., Keele, J. W., Snelling, W. M., Fox, J. M., Chitko-McKown, C. G. & other authors ( 2003; ). Prion gene sequence variation within diverse groups of U.S. sheep, beef cattle, and deer. Mamm Genome 14, 765–777.[CrossRef]
    [Google Scholar]
  21. Hill, A. F., Desbruslais, M., Joiner, S., Sidle, K. C., 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]
  22. Houston, F., Foster, J. D., Chong, A., Hunter, N. & Bostock, C. J. ( 2000; ). Transmission of BSE by blood transfusion in sheep. Lancet 356, 999–1000.[CrossRef]
    [Google Scholar]
  23. 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 [CrossRef]
    [Google Scholar]
  24. Hunter, N. ( 2003; ). Scrapie and experimental BSE in sheep. Br Med Bull 66, 171–183.[CrossRef]
    [Google Scholar]
  25. Ikeda, T., Horiuchi, M., Ishiguro, N., Muramatsu, Y., Kai-Uwe, G. D. & Shinagawa, M. ( 1995; ). Amino acid polymorphisms of PrP with reference to onset of scrapie in Suffolk and Corriedale sheep in Japan. J Gen Virol 76, 2577–2581.[CrossRef]
    [Google Scholar]
  26. Jeffrey, M., Ryder, S., Martin, S., Hawkins, S. A., Terry, L., Berthelin-Baker, C. & Bellworthy, S. J. ( 2001; ). Oral inoculation of sheep with the agent of bovine spongiform encephalopathy (BSE). 1. Onset and distribution of disease-specific PrP accumulation in brain and viscera. J Comp Pathol 124, 280–289.[CrossRef]
    [Google Scholar]
  27. Jeffrey, M., Martin, S., González, L., Foster, J., Langeveld, J. P., van Zijderveld, F. G., Grassi, J. & Hunter, N. ( 2006; ). Immunohistochemical features of PrPd accumulation in natural and experimental goat transmissible spongiform encephalopathies. J Comp Pathol 134, 171–181.[CrossRef]
    [Google Scholar]
  28. Kao, R. R., Gravenor, M. B., Baylis, M., Bostock, C. J., Chihota, C. M., Evans, J. C., Goldmann, W., Smith, A. J. & McLean, A. R. ( 2002; ). The potential size and duration of an epidemic of bovine spongiform encephalopathy in British sheep. Science 295, 332–335.[CrossRef]
    [Google Scholar]
  29. Kao, R. R., Houston, F., Baylis, M., Chihota, C. M., Goldmann, W., Gravenor, M. B., Hunter, N. & McLean, A. R. ( 2003; ). Epidemiological implications of the susceptibility to BSE of putatively resistant sheep. J Gen Virol 84, 3503–3512.[CrossRef]
    [Google Scholar]
  30. 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.[CrossRef]
    [Google Scholar]
  31. Lan, Z., Wang, Z. L., Liu, Y. & Zhang, X. ( 2006; ). Prion protein gene (PRNP) polymorphisms in Xinjiang local sheep breeds in China. Arch Virol 151, 2095–2101.[CrossRef]
    [Google Scholar]
  32. Laplanche, J. L., Chatelain, J., Westaway, D., Thomas, S., Dussaucy, M., Brugere-Picoux, J. & Launay, J. M. ( 1993; ). PrP polymorphisms associated with natural scrapie discovered by denaturing gradient gel electrophoresis. Genomics 15, 30–37.[CrossRef]
    [Google Scholar]
  33. 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.[CrossRef]
    [Google Scholar]
  34. Ohara, J., Togari, T., Kurokawa, A., Maeda, J., Ishiguro, N., Furuoka, H. & Horiuchi, M. ( 2007; ). Frequencies of PrP genotypes in meat breeds of Japanese sheep and trail of selective breeding in experimental sheep flock. J Vet Med Sci 69, 1325–1329.[CrossRef]
    [Google Scholar]
  35. Prusiner, S. B. ( 1982; ). Novel proteinaceous particles cause scrapie. Science 216, 136–144.[CrossRef]
    [Google Scholar]
  36. Ronzon, F., Bencsik, A., Lezmi, S., Vulin, J., Kodjo, A. & Baron, T. ( 2006; ). BSE inoculation to prion diseases-resistant sheep reveals tricky silent carriers. Biochem Biophys Res Commun 350, 872–877.[CrossRef]
    [Google Scholar]
  37. Saunders, G. C., Cawthraw, S., Mountjoy, S., Hope, J. & Windl, O. ( 2006; ). PrP genotypes of atypical scrapie cases in Great Britain. J Gen Virol 87, 3141–3149.[CrossRef]
    [Google Scholar]
  38. Saunders, G. C., Cawthraw, S., Mountjoy, S. J., Tout, A. C., Sayers, A. R., Hope, J. & Windl, O. ( 2009; ). Ovine PRNP untranslated region and promoter haplotype diversity. J Gen Virol 90, 1289–1293.[CrossRef]
    [Google Scholar]
  39. Serrano, C., Martín-Burriel, I., Lyahyai, J., Monzón, M., El Hamidi, M., Acín, C., Badiola, J. J., Tligui, N. & Zaragoza, P. ( 2007; ). Polymorphisms of the PRNP gene in Moroccan sheep breeds. Vet Rec 161, 524–525.[CrossRef]
    [Google Scholar]
  40. Sharpe, A., McElroy, M., Langeveld, J. P., Bassett, H., O'Donoghue, A. M. & Sweeney, T. ( 2005; ). Immunohistochemical studies of scrapie archival material from Irish ARQ/ARQ sheep for evidence of bovine spongiform encephalopathy-derived disease. Res Vet Sci 79, 29–35.[CrossRef]
    [Google Scholar]
  41. Simmons, M. M., Konold, T., Simmons, H. A., Spencer, Y. I., Lockey, R., Spiropoulos, J., Everitt, S. & Clifford, D. ( 2007; ). Experimental transmission of atypical scrapie to sheep. BMC Vet Res 3, 20 [CrossRef]
    [Google Scholar]
  42. Simmons, H. A., Simmons, M. M., Spencer, Y. I., Chaplin, M. J., Povey, G., Davis, A., Ortiz-Pelaez, A., Hunter, N., Matthews, D. & other authors ( 2009; ). Atypical scrapie in sheep from a UK research flock which is free from classical scrapie. BMC Vet Res 5, 8 [CrossRef]
    [Google Scholar]
  43. Stack, M., Jeffrey, M., Gubbins, S., Grimmer, S., González, L., Martin, S., Chaplin, M., Webb, P., Simmons, M. & other authors ( 2006; ). Monitoring for bovine spongiform encephalopathy in sheep in Great Britain, 1998–2004. J Gen Virol 87, 2099–2107.[CrossRef]
    [Google Scholar]
  44. Thuring, C. M., Erkens, J. H, Jacobs, J. G., Bossers, A., Van Keulen, L. J., Garssen, G. J., Van Zijderveld, F. G., Ryder, S. J., Groschup, M. H. & other authors ( 2004; ). Discrimination between scrapie and bovine spongiform encephalopathy in sheep by molecular size, immunoreactivity, and glycoprofile of prion protein. J Clin Microbiol 42, 972–980.[CrossRef]
    [Google Scholar]
  45. 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.[CrossRef]
    [Google Scholar]
  46. van Keulen, L. J., Vromans, M. E., Dolstra, C. H., Bossers, A. & van Zijderveld, F. G. ( 2008; ). Pathogenesis of bovine spongiform encephalopathy in sheep. Arch Virol 153, 445–453.[CrossRef]
    [Google Scholar]
  47. Ward, H. J., Everington, D., Cousens, S. N., Smith-Bathgate, B., Leitch, M., Cooper, S., Heath, C., Knight, R. S., Smith, P. G. & other authors ( 2006; ). Risk factors for variant Creutzfeldt–Jakob disease: a case–control study. Ann Neurol 59, 111–120.[CrossRef]
    [Google Scholar]
  48. Wells, G. A. H., Scott, A. C., Johnson, C. T., Gunning, R. F., Hancock, R. D., Jeffrey, M., Dawson, M. & Bradley, R. ( 1987; ). A novel progressive spongiform encephalopathy in cattle. Vet Rec 121, 419–420.[CrossRef]
    [Google Scholar]
  49. Wells, G. A. H., Konold, T., Arnold, M. E., Austin, A. R., Hawkins, S. A. C., Stack, M., Simmons, M. M., Lee, Y. H., Gavier-Widén, D. & other authors ( 2007; ). Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle. J Gen Virol 88, 1363–1373.[CrossRef]
    [Google Scholar]
  50. Wilesmith, J. W., Ryan, J. B. & Hueston, W. D. ( 1992; ). Bovine spongiform encephalopathy: case–control studies of calf feeding practices and meat and bonemeal inclusion in proprietary concentrates. Res Vet Sci 52, 325–331.[CrossRef]
    [Google Scholar]
  51. Will, R. G., Ironside, J. W., Zeidler, M., Cousens, S. N., Estibeiro, K., Alperovitch, A., Poser, S., Pocchiari, M., Hofman, A. & other authors ( 1996; ). A new variant of Creutzfeldt–Jakob disease in the UK. Lancet 347, 921–925.[CrossRef]
    [Google Scholar]
  52. Yang, S., Thackray, A. M., Fitzmaurice, T. J. & Bujdoso, R. ( 2008; ). Copper-induced structural changes in the ovine prion protein are influenced by a polymorphism at codon 112. Biochim Biophys Acta 1784, 683–692.[CrossRef]
    [Google Scholar]
  53. Zhang, L., Li, N., Fan, B., Fang, M. & Xu, W. ( 2004; ). PRNP polymorphisms in Chinese ovine, caprine and bovine breeds. Anim Genet 35, 457–461.[CrossRef]
    [Google Scholar]
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