1887

Abstract

Development of mice expressing either ovine (Tg338) or cervid (TgElk) prion protein (PrP) have aided in characterization of scrapie and chronic wasting disease (CWD), respectively. Experimental inoculation of sheep with CWD prions has demonstrated the potential for interspecies transmission but, infection with CWD versus classical scrapie prions may be difficult to differentiate using validated diagnostic platforms. In this study, mouse bioassay in Tg338 and TgElk was utilized to evaluate transmission of CWD versus scrapie prions from small ruminants. Mice (≥5 per homogenate) were inoculated with brain homogenates from clinically affected sheep or goats with naturally acquired classical scrapie, white-tailed deer with naturally acquired CWD (WTD-CWD) or sheep with experimentally acquired CWD derived from elk (sheep-passaged-CWD). Survival time (time to clinical disease) and attack rates (brain accumulation of protease resistant PrP, PrP) were determined. Inoculation with classical scrapie prions resulted in clinical disease and 100 % attack rates in Tg338, but no clinical disease at endpoint (>300 days post-inoculation, p.i.) and low attack rates (6.8 %) in TgElk. Inoculation with WTD-CWD prions yielded no clinical disease or brain PrP accumulation in Tg338 at endpoint (>500 days p.i.), but rapid onset of clinical disease (~121 days p.i.) and 100 % attack rate in TgElk. Sheep-passaged-CWD resulted in transmission to both mouse lines with 100 % attack rates at endpoint in Tg338 and an attack rate of ~73 % in TgElk with some culled due to clinical disease. These primary transmission observations demonstrate the potential of bioassay in Tg338 and TgElk to help differentiate possible infection with CWD versus classical scrapie prions in sheep and goats.

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2016-09-01
2024-10-09
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References

  1. Balachandran A., Harrington N. P., Algire J., Soutyrine A., Spraker T. R., Jeffrey M., González L., O'Rourke K. I. 2010; Experimental oral transmission of chronic wasting disease to red deer (Cervus elaphus elaphus): early detection and late stage distribution of protease-resistant prion protein. Can Vet J 51:169–178[PubMed]
    [Google Scholar]
  2. Baron T., Crozet C., Biacabe A. G., Philippe S., Verchere J., Bencsik A., Madec J. Y., Calavas D., Samarut J. 2004; Molecular analysis of the protease-resistant prion protein in scrapie and bovine spongiform encephalopathy transmitted to ovine transgenic and wild-type mice. J Virol 78:6243–6251 [View Article][PubMed]
    [Google Scholar]
  3. Beck K. E., Sallis R. E., Lockey R., Simmons M. M., Spiropoulos J. 2010; Ovine PrP genotype is linked with lesion profile and immunohistochemistry patterns after primary transmission of classical scrapie to wild-type mice. J Neuropathol Exp Neurol 69:483–497 [View Article][PubMed]
    [Google Scholar]
  4. Beck K. E., Sallis R. E., Lockey R., Vickery C. M., Béringue V., Laude H., Holder T. M., Thorne L., Terry L. A. et al. 2012a; Use of murine bioassay to resolve ovine transmissible spongiform encephalopathy cases showing a bovine spongiform encephalopathy molecular profile. Brain Pathol 22:265–279 [View Article]
    [Google Scholar]
  5. Beck K. E., Vickery C. M., Lockey R., Holder T., Thorne L., Terry L. A., Denyer M., Webb P., Simmons M. M., Spiropoulos J. 2012b; The interpretation of disease phenotypes to identify TSE strains following murine bioassay: characterisation of classical scrapie. Vet Res 43:77 [View Article]
    [Google Scholar]
  6. Beck K. E., Thorne L., Lockey R., Vickery C. M., Terry L. A., Bujdoso R., Spiropoulos J. 2013; Strain typing of classical scrapie by transgenic mouse bioassay using protein misfolding cyclic amplification to replace primary passage. PLoS One 8:e57851 [View Article][PubMed]
    [Google Scholar]
  7. Béringue V., Herzog L., Jaumain E., Reine F., Sibille P., Le Dur A., Vilotte J. L., Laude H. 2012; Facilitated cross-species transmission of prions in extraneural tissue. Science 335:472–475 [View Article][PubMed]
    [Google Scholar]
  8. 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 [View Article][PubMed]
    [Google Scholar]
  9. Bruce M. E. 2003; TSE strain variation. Br Med Bull 66:99–108 [View Article][PubMed]
    [Google Scholar]
  10. Bruce M. E., Boyle A., McConnell I. 2004; TSE strain typing in mice. In Techniques in Prion Research pp. 132–146 Edited by Lehmann S., Grassi J. Basel, Switzerland: Birkhauser Verlag; [CrossRef]
    [Google Scholar]
  11. Bruce M. E., Boyle A., Cousens S., McConnell I., Foster J., Goldmann W., Fraser H. 2002; Strain characterization of natural sheep scrapie and comparison with BSE. J Gen Virol 83:695–704 [View Article][PubMed]
    [Google Scholar]
  12. Chong A., Kennedy I., Goldmann W., Green A., González L., Jeffrey M., Hunter N. 2015; Archival search for historical atypical scrapie in sheep reveals evidence for mixed infections. J Gen Virol 96:3165–3178 [View Article][PubMed]
    [Google Scholar]
  13. Cordier C., Bencsik A., Philippe S., Bétemps D., Ronzon F., Calavas D., Crozet C., Baron T. 2006; Transmission and characterization of bovine spongiform encephalopathy sources in two ovine transgenic mouse lines (TgOvPrP4 and TgOvPrP59). J Gen Virol 87:3763–3771 [View Article][PubMed]
    [Google Scholar]
  14. Crozet C., Flamant F., Bencsik A., Aubert D., Samarut J., Baron T. 2001; Efficient transmission of two different sheep scrapie isolates in transgenic mice expressing the ovine PrP gene. J Virol 75:5328–5334 [View Article][PubMed]
    [Google Scholar]
  15. Di Bari M. A., Nonno R., Agrimi U. 2012; The mouse model for scrapie: inoculation, clinical scoring, and histopathological techniques. Methods Mol Biol 849:453–471 [View Article][PubMed]
    [Google Scholar]
  16. Douet J. Y., Lacroux C., Corbière F., Litaise C., Simmons H., Lugan S., Costes P., Cassard H., Weisbecker J. L. et al. 2014; PrP expression level and sensitivity to prion infection. J Virol 88:5870–5872 [View Article][PubMed]
    [Google Scholar]
  17. Duque Velásquez C., Kim C., Herbst A., Daude N., Garza M. C., Wille H., Aiken J., McKenzie D. 2015; Deer prion proteins modulate the emergence and adaptation of chronic wasting disease strains. J Virol 89:12362–12373 [View Article][PubMed]
    [Google Scholar]
  18. González L., Thorne L., Jeffrey M., Martin S., Spiropoulos J., Beck K. E., Lockey R. W., Vickery C. M., Holder T., Terry L. 2012; Infectious titres of sheep scrapie and bovine spongiform encephalopathy agents cannot be accurately predicted from quantitative laboratory test results. J Gen Virol 93:2518–2527 [View Article][PubMed]
    [Google Scholar]
  19. Haley N. J., Hoover E. A. 2015; Chronic wasting disease of cervids: current knowledge and future perspectives. Annu Rev Anim Biosci 3:305–325 [View Article][PubMed]
    [Google Scholar]
  20. Hamir A. N., Kunkle R. A., Cutlip R. C., Miller J. M., Williams E. S., Richt J. A. 2006; Transmission of chronic wasting disease of mule deer to Suffolk sheep following intracerebral inoculation. J Vet Diagn Invest 18:558–565 [View Article][PubMed]
    [Google Scholar]
  21. Holm S. 1979; A simple sequentially rejective multiple test procedure. Scand J Statist 6:65–70
    [Google Scholar]
  22. Jeon Y. C., Choi J. K., Choi E. K., Carp R., Kim Y. S. 2013; Pathological characterization of TgElk mice injected with brain homogenate from elk with chronic wasting disease. J Vet Sci 14:21–26 [View Article][PubMed]
    [Google Scholar]
  23. Konold T., Phelan L. 2014; Clinical examination protocol to detect atypical and classical scrapie in sheep. J Vis Expe51101 [View Article][PubMed]
    [Google Scholar]
  24. LaFauci G., Carp R., Meeker H. C., Ye X., Kim J., 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 [View Article][PubMed]
    [Google Scholar]
  25. Langevin C., Andréoletti O., Le Dur A., Laude H., Béringue V. 2011; Marked influence of the route of infection on prion strain apparent phenotype in a scrapie transgenic mouse model. Neurobiol Dis 41:219–225 [View Article][PubMed]
    [Google Scholar]
  26. Laude H., Vilette D., Le Dur A., Archer F., Soulier S., Besnard N., Essalmani R., Vilotte J. L. 2002; New in vivo and ex vivo models for the experimental study of sheep scrapie: development and perspectives. C R Biol 325:49–57 [View Article][PubMed]
    [Google Scholar]
  27. Lee Y. H., Sohn H. J., Kim M. J., Kim H. J., Park K. J., Lee W. Y., Yun E., Tark D. S., Choi Y. P. et al. 2013; Experimental chronic wasting disease in wild type VM mice. J Vet Med Sci 75:1107–1110 [View Article][PubMed]
    [Google Scholar]
  28. Mitchell G., Yogasingam N., Walther I., Balachandran A. 2015; Experimental transmission of chronic wasting disease to sheep and goats. Prion 9:S48 [CrossRef]
    [Google Scholar]
  29. O'Rourke K. I., Baszler T. V., Besser T. E., Miller J. M., Cutlip R. C., Wells G. A., Ryder S. J., Parish S. M., Hamir A. N. et al. 2000; Preclinical diagnosis of scrapie by immunohistochemistry of third eyelid lymphoid tissue. J Clin Microbiol 38:3254–3259[PubMed]
    [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 [View Article][PubMed]
    [Google Scholar]
  31. O'Rourke K. I., Zhuang D., Truscott T. C., Yan H., Schneider D. A. 2011; Sparse PrP(Sc) accumulation in the placentas of goats with naturally acquired scrapie. BMC Vet Res 7:7 [View Article][PubMed]
    [Google Scholar]
  32. O'Rourke K. I., Schneider D. A., Spraker T. R., Dassanayake R. P., Highland M. A., Zhuang D., Truscott T. C. 2012; Transmissibility of caprine scrapie in ovine transgenic mice. BMC Vet Res 8:42 [View Article][PubMed]
    [Google Scholar]
  33. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144 [View Article][PubMed]
    [Google Scholar]
  34. Race R. E., Raines A., Baron T. G., Miller M. W., Jenny A., Williams E. S. 2002; Comparison of abnormal prion protein glycoform patterns from transmissible spongiform encephalopathy agent-infected deer, elk, sheep, and cattle. J Virol 76:12365–12368 [View Article][PubMed]
    [Google Scholar]
  35. Ryou C. 2007; Prions and prion diseases: fundamentals and mechanistic details. J Microbiol Biotechnol 17:1059–1070[PubMed]
    [Google Scholar]
  36. Schneider K., Fangerau H., Michaelsen B., Raab W. H. 2008; The early history of the transmissible spongiform encephalopathies exemplified by scrapie. Brain Res Bull 77:343–355 [View Article][PubMed]
    [Google Scholar]
  37. Spraker T. R., Balachandran A., Zhuang D., O'Rourke K. 2004; Variable patterns of distribution of PrP(CWD) in the obex and cranial lymphoid tissues of Rocky Mountain elk (Cervus elaphus nelsoni) with subclinical chronic wasting disease. Vet Rec 155:295–302 [View Article][PubMed]
    [Google Scholar]
  38. Stack M. J., Balachandran A., Chaplin M., Davis L., Czub S., Miller B. 2004; The first Canadian indigenous case of bovine spongiform encephalopathy (BSE) has molecular characteristics for prion protein that are similar to those of BSE in the United Kingdom but differ from those of chronic wasting disease in captive elk and deer. Can Vet J 45:825–830[PubMed]
    [Google Scholar]
  39. Tamgüney 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 [View Article][PubMed]
    [Google Scholar]
  40. Tamgüney G., Miller M. W., Giles K., Lemus A., Glidden D., DeArmond S. J., Prusiner S. B. 2009; Transmission of scrapie and sheep-passaged bovine spongiform encephalopathy prions to transgenic mice expressing elk prion protein. J Gen Virol 90:1035–1047 [View Article][PubMed]
    [Google Scholar]
  41. Thackray A. M., Hopkins L., Spiropoulos J., Bujdoso R. 2008; Molecular and transmission characteristics of primary-passaged ovine scrapie isolates in conventional and ovine PrP transgenic mice. J Virol 82:11197–11207 [View Article][PubMed]
    [Google Scholar]
  42. Thackray A. M., Hopkins L., Lockey R., Spiropoulos J., Bujdoso R. 2011a; Emergence of multiple prion strains from single isolates of ovine scrapie. J Gen Virol 92:1482–1491 [View Article]
    [Google Scholar]
  43. Thackray A. M., Hopkins L., Lockey R., Spiropoulos J., Bujdoso R. 2011b; Propagation of ovine prions from “poor” transmitter scrapie isolates in ovine PrP transgenic mice. Exp Mol Pathol 92:167–174 [View Article]
    [Google Scholar]
  44. Thackray A. M., Lockey R., Beck K. E., Spiropoulos J., Bujdoso R. 2012; Evidence for co-infection of ovine prion strains in classical scrapie isolates. J Comp Pathol 147:316–329 [View Article][PubMed]
    [Google Scholar]
  45. Tixador P., Herzog L., Reine F., Jaumain E., Chapuis J., Le Dur A., Laude H., Béringue V. 2010; The physical relationship between infectivity and prion protein aggregates is strain-dependent. PLoS Pathog 6:e1000859 [View Article][PubMed]
    [Google Scholar]
  46. Vilotte J. L., Soulier S., Essalmani R., Stinnakre M. G., Vaiman D., Lepourry L., Da Silva J. C., Besnard N., Dawson M. et al. 2001; Markedly increased susceptibility to natural sheep scrapie of transgenic mice expressing ovine prp. J Virol 75:5977–5984 [View Article][PubMed]
    [Google Scholar]
  47. Vulin J., Beck K. E., Bencsik A., Lakhdar L., Spiropoulos J., Baron T. 2012; Selection of distinct strain phenotypes in mice infected by ovine natural scrapie isolates similar to CH1641 experimental scrapie. J Neuropathol Exp Neurol 71:140–147 [View Article][PubMed]
    [Google Scholar]
  48. Wadsworth J. D., Joiner S., Hill A. F., Campbell T. A., Desbruslais M., Luthert P. J., Collinge J. 2001; Tissue distribution of protease resistant prion protein in variant Creutzfeldt–Jakob disease using a highly sensitive immunoblotting assay. Lancet 358:171–180 [View Article][PubMed]
    [Google Scholar]
  49. Williams E. S., Young S. 1980; Chronic wasting disease of captive mule deer: a spongiform encephalopathy. J Wildl Dis 16:89–98 [View Article][PubMed]
    [Google Scholar]
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