1887

Abstract

Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative prion disease that mainly affects cattle. Transmission of BSE to humans caused a variant form of Creutzfeldt–Jakob disease. Following infection, the protease-resistant, disease-associated isoform of prion protein (PrP) accumulates in the central nervous system and in other tissues. Many countries have defined bovine tissues that may contain prions as specified risk materials, which must not enter the human or animal food chains and therefore must be discarded. Ultrasensitive techniques such as protein misfolding cyclic amplification (PMCA) have been developed to detect PrP when present in minuscule amounts that are not readily detected by other diagnostic methods such as immunohistochemistry or Western blotting. This study was conducted to determine when and where PrP can be found by PMCA in cattle orally challenged with BSE. A total of 48 different tissue samples from four cattle infected orally with BSE at various clinical stages of disease were examined using a standardized PMCA protocol. The protocol used brain homogenate from bovine PrP transgenic mice (Tgbov XV) as substrate and three consecutive rounds of PMCA. Using this protocol, PrP was found in the brain, spinal cord, nerve ganglia, optic nerve and Peyer’s patches. The presence of PrP was confirmed in adrenal glands, as well as in mesenteric lymph nodes – a finding that was reported recently by another group. Interestingly, additional positive results were obtained for the first time in the oesophagus, abomasum, rumen and rectum of clinically affected cattle.

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2012-12-01
2024-03-28
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References

  1. Balkema-Buschmann A., Eiden M., Hoffmann C., Kaatz M., Ziegler U., Keller M., Groschup M. H. 2011; BSE infectivity in the absence of detectable PrPSc accumulation in the tongue and nasal mucosa of terminally diseased cattle. J Gen Virol 92:467–476 [View Article][PubMed]
    [Google Scholar]
  2. 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 [View Article][PubMed]
    [Google Scholar]
  3. Buschmann A., Groschup M. H. 2005a; Highly bovine spongiform encephalopathy-sensitive transgenic mice confirm the essential restriction of infectivity to the nervous system in clinically diseased cattle. J Infect Dis 192:934–942 [View Article][PubMed]
    [Google Scholar]
  4. Buschmann A., Groschup M. H. 2005b; TSE eradication in small ruminants – quo vadis?. Berl Munch Tierarztl Wochenschr 118:365–371[PubMed]
    [Google Scholar]
  5. Buschmann A., Pfaff E., Reifenberg K., Müller H. M., Groschup M. H. 2000; Detection of cattle-derived BSE prions using transgenic mice overexpressing bovine PrPC . Arch Virol Suppl 16:75–86[PubMed]
    [Google Scholar]
  6. Castilla J., Saá P., Hetz C., Soto C. 2005; In vitro generation of infectious scrapie prions. Cell 121:195–206 [View Article][PubMed]
    [Google Scholar]
  7. Castilla J., Gonzalez-Romero D., Saá P., Morales R., De Castro J., Soto C. 2008; Crossing the species barrier by PrPSc replication in vitro generates unique infectious prions. Cell 134:757–768 [View Article][PubMed]
    [Google Scholar]
  8. Coenen A. M., Drinkenburg W. H., Hoenderken R., van Luijtelaar E. L. 1995; Carbon dioxide euthanasia in rats: oxygen supplementation minimizes signs of agitation and asphyxia. Lab Anim 29:262–268 [View Article][PubMed]
    [Google Scholar]
  9. Colby D. W., Wain R., Baskakov I. V., Legname G., Palmer C. G., Nguyen H. O., Lemus A., Cohen F. E., DeArmond S. J., Prusiner S. B. 2010; Protease-sensitive synthetic prions. PLoS Pathog 6:e1000736 [View Article][PubMed]
    [Google Scholar]
  10. Cosseddu G. M., Nonno R., Vaccari G., Bucalossi C., Fernandez-Borges N., Di Bari M. A., Castilla J., Agrimi U. 2011; Ultra-efficient PrPSc amplification highlights potentialities and pitfalls of PMCA technology. PLoS Pathog 7:e1002370 [View Article][PubMed]
    [Google Scholar]
  11. Eiden M., Hoffmann C., Balkema-Buschmann A., Müller M., Baumgartner K., Groschup M. H. 2010; Biochemical and immunohistochemical characterization of feline spongiform encephalopathy in a German captive cheetah. J Gen Virol 91:2874–2883 [View Article][PubMed]
    [Google Scholar]
  12. González L., Martin S., Sisó S., Konold T., Ortiz-Peláez A., Phelan L., Goldmann W., Stewart P., Saunders G. other authors 2009; High prevalence of scrapie in a dairy goat herd: tissue distribution of disease-associated PrP and effect of PRNP genotype and age. Vet Res 40:65 [View Article][PubMed]
    [Google Scholar]
  13. Gonzalez-Montalban N., Makarava N., Ostapchenko V. G., Savtchenk R., Alexeeva I., Rohwer R. G., Baskakov I. V. 2011a; Highly efficient protein misfolding cyclic amplification. PLoS Pathog 7:e1001277 [View Article][PubMed]
    [Google Scholar]
  14. Gonzalez-Montalban N., Makarava N., Savtchenko R., Baskakov I. V. 2011b; Relationship between conformational stability and amplification efficiency of prions. Biochemistry 50:7933–7940 [View Article][PubMed]
    [Google Scholar]
  15. Hamir A. N., Kehrli M. E. Jr, Kunkle R. A., Greenlee J. J., Nicholson E. M., Richt J. A., Miller J. M., Cutlip R. C. 2011; Experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle: comparison to bovine spongiform encephalopathy in cattle. J Vet Diagn Invest 23:407–420 [View Article][PubMed]
    [Google Scholar]
  16. 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, 526 [View Article][PubMed]
    [Google Scholar]
  17. Hoffmann C., Ziegler U., Buschmann A., Weber A., Kupfer L., Oelschlegel A., Hammerschmidt B., Groschup M. H. 2007; Prions spread via the autonomic nervous system from the gut to the central nervous system in cattle incubating bovine spongiform encephalopathy. J Gen Virol 88:1048–1055 [View Article][PubMed]
    [Google Scholar]
  18. Hoffmann C., Eiden M., Kaatz M., Keller M., Ziegler U., Rogers R., Hills B., Balkema-Buschmann A., van Keulen L. other authors 2011; BSE infectivity in jejunum, ileum and ileocaecal junction of incubating cattle. Vet Res 42:21 [View Article][PubMed]
    [Google Scholar]
  19. Johnson C. J., Aiken J. M., McKenzie D., Samuel M. D., Pedersen J. A. 2012; Highly efficient amplification of chronic wasting disease agent by protein misfolding cyclic amplification with beads (PMCAb). PLoS ONE 7:e35383 [View Article][PubMed]
    [Google Scholar]
  20. Jones D. M., Arters J., Berger-Sweeney J. 1999; Carbon dioxide-induced anesthesia has no effect on brain biogenic amine concentrations in mice. Lab Anim Sci 49:316–318[PubMed]
    [Google Scholar]
  21. Jones M., Peden A. H., Prowse C. V., Gröner A., Manson J. C., Turner M. L., Ironside J. W., MacGregor I. R., Head M. W. 2007; In vitro amplification and detection of variant Creutzfeldt–Jakob disease PrPSc . J Pathol 213:21–26 [View Article][PubMed]
    [Google Scholar]
  22. Kaatz M., Fast C., Ziegler U., Balkema-Buschmann A., Hammerschmidt B., Keller M., Oelschlegel A., McIntyre L., Groschup M. H. 2012; Spread of classic BSE prions from the gut via the peripheral nervous system to the brain. Am J Pathol 181:515–524 [View Article][PubMed]
    [Google Scholar]
  23. Kirkwood J. K., Wells G. A., Wilesmith J. W., Cunningham A. A., Jackson S. I. 1990; Spongiform encephalopathy in an arabian oryx (Oryx leucoryx) and a greater kudu (Tragelaphus strepsiceros). Vet Rec 127:418–420[PubMed]
    [Google Scholar]
  24. Kurt T. D., Perrott M. R., Wilusz C. J., Wilusz J., Supattapone S., Telling G. C., Zabel M. D., Hoover E. A. 2007; Efficient in vitro amplification of chronic wasting disease PrPRES. . J Virol 81:9605–9608 [View Article][PubMed]
    [Google Scholar]
  25. Makarava N., Kovacs G. G., Savtchenko R., Alexeeva I., Ostapchenko V. G., Budka H., Rohwer R. G., Baskakov I. V. 2012; A new mechanism for transmissible prion diseases. J Neurosci 32:7345–7355 [View Article][PubMed]
    [Google Scholar]
  26. Murayama Y., Yoshioka M., Yokoyama T., Iwamaru Y., Imamura M., Masujin K., Yoshiba S., Mohri S. 2007; Efficient in vitro amplification of a mouse-adapted scrapie prion protein. Neurosci Lett 413:270–273 [View Article][PubMed]
    [Google Scholar]
  27. Murayama Y., Yoshioka M., Masujin K., Okada H., Iwamaru Y., Imamura M., Matsuura Y., Fukuda S., Onoe S. other authors 2010; Sulfated dextrans enhance in vitro amplification of bovine spongiform encephalopathy PrPSc and enable ultrasensitive detection of bovine PrPSc . PLoS ONE 5:e13152 [View Article][PubMed]
    [Google Scholar]
  28. Pearson G. R., Gruffydd-Jones T. J., Wyatt J. M., Hope J., Chong A., Scott A. C., Dawson M., Wells G. A. 1991; Feline spongiform encephalopathy. Vet Rec 128:532 [View Article][PubMed]
    [Google Scholar]
  29. Pritzkow S., Wagenführ K., Daus M. L., Boerner S., Lemmer K., Thomzig A., Mielke M., Beekes M. 2011; Quantitative detection and biological propagation of scrapie seeding activity in vitro facilitate use of prions as model pathogens for disinfection. PLoS ONE 6:e20384 [View Article][PubMed]
    [Google Scholar]
  30. Richt J. A., Kasinathan P., Hamir A. N., Castilla J., Sathiyaseelan T., Vargas F., Sathiyaseelan J., Wu H., Matsushita H. other authors 2007; Production of cattle lacking prion protein. Nat Biotechnol 25:132–138 [View Article][PubMed]
    [Google Scholar]
  31. Saá P., Castilla J., Soto C. 2006; Ultra-efficient replication of infectious prions by automated protein misfolding cyclic amplification. J Biol Chem 281:35245–35252 [View Article][PubMed]
    [Google Scholar]
  32. Saborio G. P., Permanne B., Soto C. 2001; Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411:810–813 [View Article][PubMed]
    [Google Scholar]
  33. Stack M. J., Moore S. J., Vidal-Diez A., Arnold M. E., Jones E. M., Spencer Y. I., Webb P., Spiropoulos J., Powell L. other authors 2011; Experimental bovine spongiform encephalopathy: detection of PrPSc in the small intestine relative to exposure dose and age. J Comp Pathol 145:289–301 [CrossRef]
    [Google Scholar]
  34. Thorne L., Terry L. A. 2008; In vitro amplification of PrPSc derived from the brain and blood of sheep infected with scrapie. J Gen Virol 89:3177–3184 [View Article][PubMed]
    [Google Scholar]
  35. van Keulen L. J., Schreuder B. E., Vromans M. E., Langeveld J. P., Smits M. A. 2000; Pathogenesis of natural scrapie in sheep. Arch Virol Suppl 16:57–71[PubMed]
    [Google Scholar]
  36. Wells G. A., Hawkins S. A., Green R. B., Spencer Y. I., Dexter I., Dawson M. 1999; Limited detection of sternal bone marrow infectivity in the clinical phase of experimental bovine spongiform encephalopathy (BSE). Vet Rec 144:292–294 [View Article][PubMed]
    [Google Scholar]
  37. Wells G. A., Konold T., Arnold M. E., Austin A. R., Hawkins S. A., 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 [View Article][PubMed]
    [Google Scholar]
  38. Wilesmith J. W., Wells G. A., Cranwell M. P., Ryan J. B. 1988; Bovine spongiform encephalopathy: epidemiological studies. Vet Rec 123:638–644[PubMed]
    [Google Scholar]
  39. Yokoyama T., Takeuchi A., Yamamoto M., Kitamoto T., Ironside J. W., Morita M. 2011; Heparin enhances the cell-protein misfolding cyclic amplification efficiency of variant Creutzfeldt–Jakob disease. Neurosci Lett 498:119–123 [View Article][PubMed]
    [Google Scholar]
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