Prions and animal transmissible spongioform encephalopathies

Main Article Content

Polona Juntes
Jelka Zabavnik Piano
Ivan Ambrožič


Background. Transmissible spongiform encephalopathies (TSEs) or prion diseases are a unique group of neurodegenerative diseases of animals and humans, which always have a fatal outcome and are transmissible among animals of the same or different species.

Scope and Approach. The aim of this work is to review some recent data about animal TSEs, with the emphasis on their causative agents and zoonotic potential, and to discuss why the surveillance and control measures over animal TSEs should remain in force.

Key Findings and Conclusions. We still have incomplete knowledge of prions and prion diseases. Scrapie has been present for a very long time and controlled with varied success. Bovine spongiform encephalopathy (BSE) emerged unnoticed, and spread within a few years to epidemic proportions, entailing enormous economic consequences and public concerns. Currently, the classical BSE epidemic is under control, but atypical cases do, and probably will, persist in bovine populations. The Chronic Wasting Disease (CWD) of the cervids has been spreading in North America and has recently been detected in Europe. Preventive measures for the control of classical BSE remain in force, including the feed ban and removal of specified risk materials. However, active BSE surveillance has considerably decreased. In the absence of such preventive and control measures, atypical BSE cases in healthy slaughtered bovines might persist in the human food chain, and BSE prions might resurface. Moreover, other prion strains might emerge and spread undetected if the appropriate preventive and surveillance measures were to cease, leaving behind inestimable consequences.


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Juntes, P., Zabavnik Piano, J., & Ambrožič, I. (2017). Prions and animal transmissible spongioform encephalopathies. Veterinarski Glasnik, 71(1), 1-15.
Author Biography

Jelka Zabavnik Piano, University of Ljubljana, Veterinary Faculty

Institute of Preclinical Sciences


Alberti, S., Halfmann, R., King, O., Kapila, A., Lindquist, S. 2009. A systematic survey identifies prions and illuminates sequence features of prionogenic proteins. Cell 137:146–158. doi:10.1016/j.cell.2009.02.044

Andréoletti, O., Litaise C., Simmons, H., Corbière F., Lugan, S., Costes, P., Schelcher, F., Vilette, D., Grassi, J., Lacroux, C. 2012. Highly efficient prion transmission by blood transfusion. PloS Pathogens 8:e1002782; http_//

Angers, R. C., Browning, S. R., Seward, T. S., Sigurdson, C. J., Miller, M. W., Hoover, E. A., Telling, G. C. 2006. Prions in skeletal muscles of deer with chronic wasting disease. Science 311:1117. doi: 10.1126/science.1122864.

Angers, R. C., Seward, T. S., Napier, D., Green, M., Hoover, E., Spraker, T., O'Rourke, K., Balachandran, A., Telling, G. C. 2009. Chronic wasting disease prions in elk antler velvet. Emerging and Infectious Diseases 15:696-703. doi: 10.3201/eid1505.081458.

Atkinson, C. J., Zhang, K., Munn, A. L., Wiegmans, A., Wei, M. G. 2016. Prion protein scrapie and the normal cellular prion protein. Prion 10:63-82. doi: 10.1080/19336896.2015.1110293.

Barria, M. A., Ironside, J. W., Head, M. W. 2014. Exploring the zoonotic potential of animal prion diseases. Prion 8:1, 85-91. doi: 10.4161/pri.28124.

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. Veterinary Record 153(7):202-208. doi:10.1136/vr.153.7.202

Benestad, S. L., Arsac, J. N., Goldmann, W., Nöremark, M. 2008. Atypical/NOR98 scrapie: properties of the agent, genetics, and epidemiology. Veterinary Research 39(4):19. doi: 10.1051/vetres:2007056.

Benestad, S. L., Mitchell, G., Simmons, M., Ytrehus, B., Vikøren, T. 2016. First case of chronic wasting disease in Europe in a Norwegian free-ranging reindeer. Veterinary Research 47:88. doi: 10.1186/s13567-016-0375-4.

Béringue, V., Herzog, L., Reine, F., Le Dur, A., Casalone, C., Vilotte, J. L., Laude, H. 2008. Transmission of atypical bovine prions to mice transgenic for human prion protein. Emerging and Infectious Diseases 14:1898-1901. doi: 10.3201/eid1412.080941.

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. Journal of Virology 74(3):1407-1414.

Bucalossi, C., Cosseddu, G. M., D’Agostino, C., Di Bari, M. A., Chiappini, B., Conte, M., Rosone, F., De Grossi, L., Scavia, G., Agrimi, U., Nonno, R., Vaccari, G. 2011. Assessment of the genetic susceptibility of sheep to scrapie by protein misfolding cyclic amplification and comparison with experimental scrapie transmission studies. Journal of Virology 85(16):8386-8392.

Cassard, H., Torres, J.-M., Lacroux, C., Douet, J.-Y., Benestad, S., Lantier, F., Lugan, S., Lantier, I., Costes, P., Aron, N., Reine, F., Herzog, L., Espinosa, J.-C., Beringue, V., Andréoletti, O. 2014. Evidence for zoonotic potential of ovine scrapie prions. Nature Communications December 2014, 5, article 5821. doi: 10.1038/10.1038/NCOMMS6821.

Chakrabortee, S., Kayatekin, C., Newby, G. A., Mendillo, M. L., Lancaster, A., Lindquist, S. 2016. Luminidependens (LD) is and Arabidopsis protein with prion behaviour. Proceedings of the National Academy of Sciences 113:6065-6070. doi: 10.1073/pnas.1604478113.

Comoy, E. E., Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andréoletti, O., Cassalone, C., Richt, J. A., Greenlee, J. J., Baron, T., Benestad, S. L., Brown, P., Deslys, J.-P. 2015. Transmission of scrapie prions to primate after and extended silent incubation period. Scientific Reports 5, Article number:11573, 11 pp. doi: 10.1038/srep11573.

Černilec, M., Vranac, T., Hafner-Bratkovič, I., Koren, S., Colja Venturini, A., Popović, M., Juntes P., and V. Čurin Šerbec. 2007. Identification of an epitope on the recombinant bovine PrP that is able to elicit a prominent immune response in wild-type mice. Immunology Letters 113:29-39. doi: 10.1016/j.imlet.2007.07.012.

Diack, A. B., Head, M. W., McCutcheon, S., Boyle, A., Knight, R., Ironside, J. W., Manson, J. C., Will, R. G. 2014. Variant CJD. 18 years of research and surveillance. Prion 8:286-295. doi: 10.4161/pri.2937.

European Food Safety Authority. EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards). 2011. Joint Scientific Opinion on any possible epidemiological or molecular association between TSEs in animals and humans. EFSA Journal 9(1):1945, 111 pp. doi:10.2903/j.efsa.2011.1945.

European Food Safety Authority. EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards). 2015. Scientific Opinion on request for a review of a scientific publication concerning the zoonotic potential of ovine scrapie prions. EFSA Journal 13(8):4197, 58 pp. doi:10.2903/j.efsa.2015.4197

European Food Safety Authority. EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards). 2016. The European Union summary report on data of the surveillance of ruminants for the presence of transmissible spongiform encephalopathies (TSEs) in 2015. EFSA Journal 14(12):4643 [62 pp.]. doi: 10.2903/j.efsa.2016.4643.

European Food Safety Authority. EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards). 2017. Scientific Opinion. Chronic wasting disease (CWD) in cervids. EFSA Journal 15(1):4667, 62 pp. doi:10.2903/j.efsa.2017.4667.

European Union. 2001. Regulation (EC) No 999/2001 of the European Parliament and of the Council of 22 May 2001 laying down rules for the prevention, control and eradication of certain transmissible spongiform encephalopathies. Official Journal of the European Union, L 147:1-40.

Fediaevsky, A., Tongue, S.C., Noremark, M., Calavas, D., Ru G., Hopp, P. A. 2008. A descriptive study of the prevalence of atypical and classical scrapie in sheep in 20 European countries. BMC Veterinary Research 4:19. doi: 10.1186/1746-6148-4-19.

Fast, C., Groschup, M. H. 2013. Classical and atypical scrapie in sheep and goats. In Prions and Diseases: Volume 2, Animals, Humans and Environment. Eds. W.-Q. Zou, P. Gambetti, Springer Science+Business Media, New York, pp. 15-44. doi 10.1007/978-1-4614-5338-3_2.

Gill, O. N., Spencer, Y., Richard-Loendt, A., Kelly, C., Dabaghian, R., Boyes, L., Linehan, J., Simmons, M., Webb, P., Bellerby, P., Andrews, N., Hilton, D. A., Ironside, J. W., Beck, J., Poluter, M., Mead, S. 2013. Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. British Medical Journal 347: f5675. doi:

González, L., Martin, S., Hawkins, S. A. C., Goldmann, W., Jeffrey, M., Sisó, S. 2010. Pathogenesis of natural goat scrapie: modulation by host PRNP genotype and effect of co-existent conditions. Veterinary Research 41(4):48. doi: 10.1051/vetres/2010020.

Gorjanc, G., Plohl, M., Kompan, D. 2008. Calculation of PrP genotype and NSP type probabilities in Slovenian sheep. Acta Agriculturae Slovenica 92(2):119-130.

Gough, K. C., Maddison, B. C. 2010. Prion transmission: prion excretion and occurrence in the environment. Prion 4:275-82. doi: 10.4161/pri.4.4.13678.

Haley, N. J., Seelig, D. M., Zabel, M. D., Telling, G. C., Hoover, E. A. 2009. Detection of CWD prions in urine and saliva of deer by transgenic mouse bioassay. PLoS One 4:e4848. doi: 10.1371/journal.pone.0004848.

Haley, N. J., Hoover, E. A. 2015. Chronic wasting disease of cervids: current knowledge and future perspectives. Annual Review of Animal Biosciences 3:305-325. doi: 10.1146/annurev-animal-022114-111001.

Hamir, A. N., Kehrli, M. E., 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. Journal of Veterinary Diagnostic Investigation 23(3):407-420. doi: 10.1177/1040638711403404.

Hilton, D. A., Ghani, A. C., Conyers, L., Edwards, P., McCardle, L., Penney, M., Ritchie, D., Ironside, J. W. 2002. Accumulation of prion protein in tonsil and appendix; review of tissue samples. British Medical Journal 325:633-634. doi:

Hunter, N. 2007. Scrapie – Uncertainties, biology and molecular approaches. Biochimica et Biophysica Acta 1772(6):619-628.

Juntes, P., Zabavnik Piano, J., Čurin-Šerbec, V., Kovač, Z., Pogačnik, M. 2002. Nevropatološke spremembe pri prvem primeru goveje spongiformne encefalopatije v Sloveniji (Neuropathological lesions in the first case of bovine spongiform encephalopathy in Slovenia). Slovenian Veterinary Research 39(2):105-114.

Juntes, P., Zabavnik Piano, J., Cotman, M., Ambrožič, I. 2010. Characterization of cases of ovine atypical scrapie in Slovenia. Journal of Comparative Pathology 143(4):327.

Kim, T-Y., Shon, H-J., Joo, Y-S., Mun, U-K., Kang, K-S., Lee, Y-S. 2005. Additional Cases of Chronic Wasting Disease in Imported Deer in Korea. Journal of Veterinary Medical Science 67(8):753–759.

Konold, T., Bone, G. E., Clifford, D., Chaplin, M. J., Cawthraw, S., Stack, M. J., Simmons M. M. 2012. Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges. BMC Veterinary Research 8:22 (14 pp). doi: 10.1128/JVI.02316-15.

Kuczius, T., Wohlers, J., Karch, H., Groschup, M. H. 2011. Subtyping of human cellular prion proteins and their differential solubility. Experimental Neurology 227:188-194. doi: 10.1016/j.expneurol.2010.10.014.

Kuczius, T., Groschup, M. H. 2013. Cellular prion proteins in humans and cattle but not sheep are characterized by a low-solubility phenotype. Comparative Immunology, Microbiology and Infectious Diseases 36:599-605.

Kupfer, L., Eiden, M., Buschmann, A., Groschup, M. H. 2007. Amino acid sequence and prion strain specific effects on the in vitro and in vivo convertibility of ovine/murine and bovine/murine prion protein chimeras. Biochimica et Biophysica Acta1772:704-713.

Kuznetsova, A., McKenzie, D., Banser, P., Siddique, T., Aiken, J. M. 2014. Potential role of soil properties in the spread of CWD in western Canada. Prion 8:92-9.

Langeveld, J. P. M., Erkens, J. H. F., Rammel, I., Jacobs, J. G., Davidse, A., van Zijderveld, F. G., Bossers, A., Schildorfer, H. 2011. Four independent molecular prion parameters for discriminating new cases of C, L and H bovine spongiform encephalopathy in cattle. Journal of Clinical Microbiology 49(8):3026-3028. doi: 10.1128/JCM.01102-11.

Langeveld, J. P. M., Jacobs, J. G., Hunter, N., van Keulen, L. J. M., Lantier, F., van Zijderveld, F. G., Bossers, A. 2016. Prion type-dependent deposition of PRNP allelic products in heterozygous sheep. Journal of Virology 90(2):805-812. doi: 10.1128/JVI.02316-15.

Li, A., Dong, J., Harris, D. A. 2004. Cell surface expression of the prion protein in yeast does not alter copper utilization phenotypes. Journal of Biological Chemistry 279:29469–29477. doi: 10.1074/jbc.C500058200.

Mathiason, C. K., Powers, J. G., Dahmes, S. J., Osborn, D. A., Miller, K. V., Warren, R. J., Mason, G. L., Hays, S. A., Hayes-Klug, J., Seelig, D. M., Wild, M. A., Wolfe, L. L., Spraker, T. R., Miller, M. W., Sigurdson, C. J., Telling, G. C., Hoover, E. A. 2006. Infectious prions in the saliva and blood of deer with chronic wasting disease. Science 314:133-136. doi: 10.1126/science.1132661.

Masujin, K., Okada, H., Miyazawa, K., Matsuura, Y., Imamura, M., Iwamaru, Y., Murayama, Y., Yokoyama, T. 2016. Emergence of a novel bovine spongiform encephalopathy (BSE) prion from an atypical H-type BSE. Scientific Reports 6, Article number 22753, 10 pp. doi: 10.1038/srep22753.

Melchior, M. B., Windig, J. J., Hagenaars, T. J., Bossers, A., Davidse, A., van Zijderveld, F. G. 2010. Eradication of scrapie with selective breeding: are we nearly there? MBC Veterinary Research 6:24 (9 pp). doi: 10.1186/1746-6148-6-24.

Mok, T., Jaunmuktane, Z., Joiner, S., Campbell, T., Morgan, C., Wakerley, B., Golestani, F., Rudge, P., Mead, S., Jäger, H. R., Wadsworth, J. D. F., Brandner, S., Collinge, J. 2017. Variant Creutzfeldt-Jakob Disease in a patient with heterozygosity at PRNP codon 129. New England Journal of Medicine 376:292-294. doi: 10.1056/NEJMc1610003.

Moore, S. J., Smith, J. D., Greenlee, M. H., Nicholson, E. M., Richt, J. A., Greenlee, J. J. 2016. Comparison of two US sheep scrapie isolates supports identification as separate strains. Veterinary Pathology 53(6):1187-1196.

Morales, R., Abid, K., Soto, C. 2007. The prion strain phenomenon: Molecular basis and unprecedented features. Biochimica et Biophysica Acta 1772:681-691. doi:10.1016/j.bbadis.2006.12.006.

Morales, R., Duran-Aniotz, C., Diaz-Espinoza, R., Camacho, M. V., Soto, C. 2012. Protein misfolding cyclic amplification of infectious prions. Nature Protocols 7(7):1397-1409. doi: 10.1039/nprot.2012.067.

Nalls, A. V., McNulty, E., Powers, J., Seelig, D. M., Hoover, C., Haley, N. J., Hayes-Klug, J., Anderson, K., Stewart, P., Goldmann, W., Hoover, E. A., Mathiason, C. K. 2013. Mother to Offspring Transmission of Chronic Wasting Disease in Reeves’ Muntjac Deer. PLoS One 8(8):e71844. doi:10.1371/journal.pone.0071844.

Nichols, T. A., Pulford, B., Wyckoff, A. C., Meyerett, C., Michel, B., Gertig, K., Hoover E. A., Jewell J. E., Telling G. C., Zabel M. D. 2009. Detection of protease-resistant cervid prion protein in water from a CWD-endemic area. Prion 3:171-183. doi: 10.4161/pri.3.3.9819.

OIE: Animal health in the world. Number of reported cases of bovine spongiform encephalopathy (BSE) in farmed cattle worldwide (excluding the United Kingdom). Accessed 23.2.2017a.

OIE: Animal health in the world. Number of cases of bovine spongiform encephalopathy (BSE) reported in the United Kingdom. Accessed 23.2.2017b.

OIE: Bovine spongiform encephalopathy. Manual of diagnostic tests and vaccines for terrestrial animals 2016a. Available at Accessed 23.2.2017.

OIE: Scrapie. Manual of diagnostic tests and vaccines for terrestrial animals 2016b. Available at Accessed 23.2.2017.

Peretz, D., Williamson, R. A., Legname, G., Matsunaga, Y., Vergara, J., Burton, D. R., DeArmond S. J., Prusiner S. B., Scott M. R. 2002. A change in the conformation of prions accompanies the emergence of a new prion strain. Neuron 34(6):921–932.

Prusiner, S. B. 1982. Novel proteinaceous infectious particle cause scrapie. Science 216:136-144. DOI: 10.1126/science.6801762.

Race, B. L., Meade-White, K. D., Ward, A., Jewell, J., Miller, M. W., Williams, E. S., Chesebro, B., Race, R. E. 2007. Levels of abnormal prion protein in deer and elk with chronic wasting disease. Emerging and Infectious Diseases 13:824-830. doi: 10.3201/eid1306.070186.

Saunders, S. E., Bartelt-Hunt, S. L., Bartz, J. C. 2012. Occurrence, transmission, and zoonotic potential of chronic wasting disease. Emerging and Infectious Diseases 18:369-376.

Schneider, K., Fangerau, H., Michaelsen, B., Raab, W. H.-M. 2008. The early history of transmissible spongiform encephalopathies exemplified by scrapie. Brain Research Bulletin 77(6):343-355.

Solforosi, L., Milani, M., Mancini, N., Clementi, M., Burioni, R. 2013. A closer look at prion strains. Characterisation and important implications. Prion 7:99-108. doi: 10.4161/pri.23490.

Soto, C., Satani, N. 2011. The intricate mechanisms of neurodegeneration in prion diseases. Trends in Molecular Medicine 17(1):14-24. doi:10.1016/j.molmed.2010.09.001.

Spiropoulos, J., Simmons, M. M. 2017. Pathology of animal transmissible spongiform encephalopathies (TSEs). Food Safety 5(1):1-9 (published in advance). doi: 10.14252/foodsafetyfscj.2016027.

Šnajder, M., Vilfan, T., Černilec, M., Rupreht, R., Popović, M., Juntes, P., Čurin-Šerbec, V., Poklar Ulrih, N. Enzymatic degradation of PrPSc by a protease secreted from Aeropyrum pernix K1. 2012. PloS One 7(6): 1-12; e39548. doi: 10.1371/journal.pone.0039548.

Tamgüney, G., Miller, M. W., Wolfe, L. L., Sirochman, T. M., Glidden, D. V., Palmer, C., Lemus, A., DeArmond, S. J., Prusiner, S. B. 2009. Asymptomatic deer excrete infectious prions in faeces. Nature 461:529-532. doi: 10.1038/nature08289.

Tanaka, M., Chien, P., Naber, N., Cooke, R., Weissman, J. S. 2004. Conformational variations in an infectious protein determine prion strain differences. Nature 428:323-328.

Telling, G. C. 2004. The mechanism of prion strain propagation. Genome Biology 5(5): article 222. doi: 10.1186/gb-2004-5-5-222.

Velásquez, C. D., 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. Journal of Virology 89(24):12362-12373. doi: 10.1128/JVI.02010-15.

VKM. Report from the Norwegian Scientific Committee for Food Safety (VKM). CWD in Norway. 2016. Opinion of the Panel on biological hazards, ISBN: 978-82-8259-216-1, Oslo, Norway. 2016:26, 75 pp.

Watts, C. J., Westaway, D. 2007. The prion protein family: Diversity, rivalry, and disfunction. Biochimica et Biophysica Acta 1772:654-672. doi:10.1016/j.bbadis.2007.05.001.

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. Veterinary Record 121(18):419-420.

Will, R. D., Ironside, J. W., Zeidler, M., Cousens, S. N., Estibeiro, K., Aleprovitch, A., Poser, S., Pocciari, M., Hofman, A., Smith, P. G. 1996. A new variant of Creutzfeldt-Jakob disease in UK. Lancet 347:921-925.

Williams, E. S., Young, S. 1980. Chronic wasting disease of captive mule deer: a spongiform encephalopathy. Journal of Wildlife Diseases 1980; 16:89-98.

Williams, E. S. 2005. Chronic wasting disease. Veterinary Pathology 42:530-549. doi: 10.1354/vp.42-5-530.

Wilson, R., Plinston, C., Hunter, N., Casalone, C., Corona, C., Tagliavini, F., Suardi, S., Ruggerone, M., Moda, F., Graziano, S., Sbriccoli, M., Cardone, F., Pocchiari, M., Ingrosso, L., Baron, T., Richt, J., Andreoletti, O., Simmons, M, Lockey, R., Manson, J. C., Barron, R. M. 2012. Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein. Journal of General Virology 93:1624-1629.

Wood, J. L., Lund, L. J., Done, S. H. 1992. The natural occurrence of scrapie in moufflon. Veterinary Record 130(2):25-27.

Yuan, A. H., Hohschild, A. 2017. A bacterial global regulator forms a prion. Science 355:198-201.

Zabavnik Piano, J., Cotman, M., Pogačnik, M., Juntes, P. 2004. Scrapie susceptibility-linked polymorphisms of the prion protein gene in Istrian Pramenka sheep. Slovenian Veterinary Research 41(2):105-114.

Zabavnik Piano, J., Cotman, M., Juntes, P., Ambrožič, I. 2011. Genotipi gena za prionski protein (PRNP) pri kozah v tropu s praskavcem. (Prion protein gene (PRNP) genotypes in goats from herd with scrapie). Slovenian Veterinary Research 48 (suppl. 13):229-232.

Zabavnik Piano, J., Cotman, M., Ambrožič, I., Juntes, P. 2016. Genotipigenazaprionski protein priovcah z atipičnimpraskavcem v Sloveniji (Genotypes of prion protein gene in sheep with atypical scrapie in Slovenia). Slovenian Veterinary Research 53 (suppl. 17):92-95.