1887

Abstract

A scrapie-positive ewe was found in a flock that had been scrapie-free for 13 years, but housed adjacent to scrapie-positive animals, separated by a wire fence. Live animal testing of the entire flock of 24 animals revealed seven more subclinical scrapie-positive ewes. We hypothesized that they may have contracted the disease from scrapie-positive rams used for breeding 4 months prior, possibly through the semen. The genotypes of the ewe flock were highly scrapie-susceptible and the rams were infected with the ‘Caine’ scrapie strain having a short incubation time of 4.3–14.6 months in sheep with 136/171 VQ/VQ and AQ/VQ genotypes. PrP accumulates in a variety of tissues in addition to the central nervous system. Although transmission of prion diseases, or transmissible spongiform encephalopathies, has been achieved via peripheral organ or tissue homogenates as well as by blood transfusion, neither infectivity nor PrP have been found in semen from scrapie-infected animals. Using serial protein misfolding cyclic amplification followed by a surround optical fibre immunoassay, we demonstrate that semen from rams infected with a short-incubation-time scrapie strain contains prion disease-associated-seeding activity that generated PrP in sPMCA (serial protein misfolding cyclic amplification). Injection of the ovinized transgenic mouse line TgSShpPrP with semen from scrapie-infected sheep resulted in PrP-seeding activity in clinical and, probably as a result of the low titre, non-clinical mouse brain. These results suggest that the transmissible agent, or at least the seeding activity, for sheep scrapie is present in semen. This may be a strain-specific phenomenon.

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2012-06-01
2024-03-28
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References

  1. Baylis M., Goldmann W., Houston F., Cairns D., Chong A., Ross A., Smith A., Hunter N., McLean A. R. 2002; Scrapie epidemic in a fully PrP-genotyped sheep flock. J Gen Virol 83:2907–2914[PubMed]
    [Google Scholar]
  2. Baylis M., Chihota C., Stevenson E., Goldmann W., Smith A., Sivam K., Tongue S., Gravenor M. B. 2004; Risk of scrapie in British sheep of different prion protein genotype. J Gen Virol 85:2735–2740 [View Article][PubMed]
    [Google Scholar]
  3. Belt P. B. G. M., Muileman I. H., Schreuder B. E. C., Bos-de Ruijter J., Gielkens A. L. J., Smits M. A. 1995; Identification of five allelic variants of the sheep PrP gene and their association with natural scrapie. J Gen Virol 76:509–517 [View Article][PubMed]
    [Google Scholar]
  4. Bendheim P. E., Brown H. R., Rudelli R. D., Scala L. J., Goller N. L., Wen G. Y., Kascsak R. J., Cashman N. R., Bolton D. C. 1992; Nearly ubiquitous tissue distribution of the scrapie agent precursor protein. Neurology 42:149–156[PubMed] [CrossRef]
    [Google Scholar]
  5. Bolton D. C., McKinley M. P., Prusiner S. B. 1982; Identification of a protein that purifies with the scrapie prion. Science 218:1309–1311 [View Article][PubMed]
    [Google Scholar]
  6. Bulgin M. S., Sorensen S. J., Matlock M. E. 2006; Association between incubation time and genotype in sheep experimentally inoculated with scrapie-positive brain homogenate. Am J Vet Res 67:498–504 [View Article][PubMed]
    [Google Scholar]
  7. Capellari S., Zaidi S. I., Long A. C., Kwon E. E., Petersen R. B. 2000; The Thr183Ala mutation, not the loss of the first glycosylation site, alters the physical properties of the prion protein. J Alzheimers Dis 2:27–35[PubMed]
    [Google Scholar]
  8. Chang B., Gray P., Piltch M., Bulgin M. S., Sorensen-Melson S., Miller M. W., Davies P., Brown D. R., Coughlin D. R., Rubenstein R. 2009; Surround optical fiber immunoassay (SOFIA): an ultra-sensitive assay for prion protein detection. J Virol Methods 159:15–22 [View Article][PubMed]
    [Google Scholar]
  9. Collinge J. 2001; Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci 24:519–550 [View Article][PubMed]
    [Google Scholar]
  10. Detwiler L. A., Baylis M. 2003; The epidemiology of scrapie. Rev Sci Tech 22:121–143[PubMed]
    [Google Scholar]
  11. Ecroyd H., Belghazi M., Dacheux J. L., Gatti J. L. 2005; The epididymal soluble prion protein forms a high-molecular-mass complex in association with hydrophobic proteins. Biochem J 392:211–219 [View Article][PubMed]
    [Google Scholar]
  12. EFSA Panel on Biological Hazards (BIOHAZ) 2010; Scientific opinion on risk of transmission of TSEs via semen and embryo transfer in small ruminants (sheep and goats). EFSA Journal 8:1429
    [Google Scholar]
  13. Elsen J. M., Amigues Y., Schelcher F., Ducrocq V., Andreoletti O., Eychenne F., Tien Khang J. V., Poivey J. P., Lantier F., Laplanche J. L. 1999; Genetic susceptibility and transmission factors in scrapie: detailed analysis of an epidemic in a closed flock of Romanov. Arch Virol 144:431–445 [View Article][PubMed]
    [Google Scholar]
  14. Gatti J.-L., Métayer S., Moudjou M., Andréoletti O., Lantier F., Dacheux J.-L., Sarradin P. 2002; Prion protein is secreted in soluble forms in the epididymal fluid and proteolytically processed and transported in seminal plasma. Biol Reprod 67:393–400 [View Article][PubMed]
    [Google Scholar]
  15. 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 [View Article][PubMed]
    [Google Scholar]
  16. Hamir A. N., Richt J. A., Kunkle R. A., Greenlee J. J., Bulgin M. S., Gregori L., Rohwer R. G. 2009; Characterization of a US sheep scrapie isolate with short incubation time. Vet Pathol 46:1205–1212 [View Article][PubMed]
    [Google Scholar]
  17. Hunter N. 1996; Prion protein (PRNP) genotypes and natural scrapie in closed flocks of Cheviot and Suffolk sheep in Britain. In Transmissible Subacute Spongiform Encephalopathies: Prion Diseases pp. 47–50 Edited by Court L., Dodet. B. Elsevier;
    [Google Scholar]
  18. 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 [View Article][PubMed]
    [Google Scholar]
  19. 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 [View Article][PubMed]
    [Google Scholar]
  20. Lee I. Y., Westaway D., Smit A. F. A., Wang K., Seto J., Chen L., Acharya C., Ankener M., Baskin D. other authors 1998; Complete genomic sequence and analysis of the prion protein gene region from three mammalian species. Genome Res 8:1022–1037[PubMed] [CrossRef]
    [Google Scholar]
  21. Moudjou M., Frobert Y., Grassi J., La Bonnardière C. 2001; Cellular prion protein status in sheep: tissue-specific biochemical signatures. J Gen Virol 82:2017–2024[PubMed]
    [Google Scholar]
  22. National Scrapie Surveillance Plan. 2010 National scrapie_surv_plan.pdf (page 7, point 2). Updated September
  23. Palmer A. C. 1959; Attempt to transmit scrapie by injection of semen from an affected ram. Vet Rec 71:664
    [Google Scholar]
  24. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144 [View Article][PubMed]
    [Google Scholar]
  25. Rubenstein R., Chang B., Gray P., Piltch M., Bulgin M. S., Sorensen-Melson S., Miller M. W. 2010; A novel method for preclinical detection of PrPSc in blood. J Gen Virol 91:1883–1892 [View Article][PubMed]
    [Google Scholar]
  26. Rubenstein R., Chang B., Gray P., Piltch M., Bulgin M. S., Sorensen-Melson S., Miller M. W. 2011; Prion disease detection, PMCA kinetics, and IgG in urine from sheep naturally/experimentally infected with scrapie and deer with preclinical/clinical chronic wasting disease. J Virol 85:9031–9038 [View Article][PubMed]
    [Google Scholar]
  27. Sarradin P., Melo S., Barc C., Lecomte C., Andréoletti O., Lantier F., Dacheux J.-L., Gatti J.-L. 2008; Semen from scrapie-infected rams does not transmit prion infection to transgenic mice. Reproduction 135:415–418 [View Article][PubMed]
    [Google Scholar]
  28. Scott M. R. D., Butler D. A., Bredesen D. E., Wälchli M., Hsiao K. K., Prusiner S. B. 1988; Prion protein gene expression in cultured cells. Protein Eng 2:69–76 [View Article][PubMed]
    [Google Scholar]
  29. Scrapie Eradication Uniform Methods and Rules 2005 Umr_scrapie.pdf. (page 47, point 6). Updated June 1
  30. Shaked Y., Rosenmann H., Talmor G., Gabizon R. 1999; A C-terminal-truncated PrP isoform is present in mature sperm. J Biol Chem 274:32153–32158 [View Article][PubMed]
    [Google Scholar]
  31. Wang S., Foote W. C., Sutton D. L., Maciulis A., Miller J. M., Evans R. C., Holyoak G. R., Call J. W., Bunch T. D. other authors 2001; Preventing experimental vertical transmission of scrapie by embryo transfer. Theriogenology 56:315–327 [View Article][PubMed]
    [Google Scholar]
  32. Wang S., Cockett N. E., Miller J. M., Shay T. L., Maciulis A., Sutton D. L., Foote W. C., Holyoak G. R., Evans R. C. other authors 2002; Polymorphic distribution of the ovine prion protein (PrP) gene in scrapie-infected sheep flocks in which embryo transfer was used to circumvent the transmissions of scrapie. Theriogenology 57:1865–1875 [View Article][PubMed]
    [Google Scholar]
  33. Weissmann C. 2004; The state of the prion. Nat Rev Microbiol 2:861–871 [View Article][PubMed]
    [Google Scholar]
  34. Westaway D., Zuliani V., Cooper C. M., Da Costa M., Neuman S., Jenny A. L., Detwiler L., Prusiner S. B. 1994; Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie. Genes Dev 8:959–969 [View Article][PubMed]
    [Google Scholar]
  35. Wrathall A. E., Brown K. F. D., Sayers A. R., Wells G. A. H., Simmons M. M., Farrelly S. S. J., Bellerby P., Squirrell J., Spencer Y. I. other authors 2002; Studies of embryo transfer from cattle clinically affected by bovine spongiform encephalopathy (BSE). Vet Rec 150:365–378 [View Article][PubMed]
    [Google Scholar]
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