Chapter 7 : Transmissible Spongiform Encephalopathies

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There are specific transmissible spongiform encephalopathies (TSEs) which affect humans and others which affect animals. Evidence suggests that bovine spongiform encephalopathy (BSE) has crossed the species barrier to cause variant Creutzfeldt-Jakob disease (vCJD) in humans. The primary focus of this chapter is on BSE and its assumed relationship with vCJD. The chapter also provides more detailed summaries on scrapie and chronic wasting disease (CWD). The clinical, pathological, and molecular genetic features of the transmissible spongiform encephalopathies have led to speculation on the nature of the etiologic agent and the pathogenic mechanisms of the disease. A transmissible spongiform encephalopathy has been diagnosed in eight species of captive wild ruminants as well as exotic (cheetahs, pumas, a tiger, and an ocelot) and domestic cats. Isolations from the distal ileum were made in experimentally infected calves that were 4 months old, at 10,14, and 18 months after dosing. This study has also identified infectivity in bone marrow, trigeminal ganglion, dorsal root ganglion, brain, and spinal cord. The diagnosis of BSE is based on the occurrence of clinical signs of the disease and currently is confirmed by postmortem histopathological examination of brain tissue. Due to the many unknowns surrounding CWD, much research is under way to better characterize the disease, determine host range, develop and validate diagnostic tests, and understand the epidemiology. The results of this work will assist in developing science-based methods for prevention and control.

Citation: Detwiler L, Rubenstein R, Williams E. 2000. Transmissible Spongiform Encephalopathies, p 131-159. In Brown C, Bolin C (ed), Emerging Diseases of Animals. ASM Press, Washington, DC. doi: 10.1128/9781555818050.ch7

Key Concept Ranking

Transmissible Spongiform Encephalopathies
Immune Systems
Chronic Wasting Disease
Prion Proteins
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Image of Figure 1
Figure 1

Number of confirmed cases of BSE in Great Britain by year of restriction, 1986 through 1999. The data include 46 cases that were not subject to official restrictions and were identified by proactive surveillance or at autopsy. Source: United Kingdom Ministry of Agriculture, Fisheries and Food.

Citation: Detwiler L, Rubenstein R, Williams E. 2000. Transmissible Spongiform Encephalopathies, p 131-159. In Brown C, Bolin C (ed), Emerging Diseases of Animals. ASM Press, Washington, DC. doi: 10.1128/9781555818050.ch7
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Image of Figure 2
Figure 2

Number of bovine brains submitted for BSE testing, by state, from 10 May 1990 through 31 March 2000. None tested positive for BSE. Source: National Veterinary Services Laboratory, APHIS, USDA.

Citation: Detwiler L, Rubenstein R, Williams E. 2000. Transmissible Spongiform Encephalopathies, p 131-159. In Brown C, Bolin C (ed), Emerging Diseases of Animals. ASM Press, Washington, DC. doi: 10.1128/9781555818050.ch7
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1. Baker, H. F.,, R. M. Ridley,, and G. A. H. Wells. 1993. Experimental transmission of BSE and scrapie to the common marmoset. Vet. Rec. 132:403406.
2. Barlow, R. M.,, and D. J. Middleton. 1990. Dietary transmission of bovine spongiform encephalopathy to mice. Vet. Rec. 126:111112.
3. Bellinger Kawahara, C. G.,, J. E. Cleaver,, T. O. Diener,, and S. B. Prusiner. 1987. Purified scrapie prions resist inactivation by UV irradiation. J. Virol. 61:159166.
4. Bellinger Kawahara, C. G.,, T. O. Diener,, M. P. McKinley,, D. F. Groth,, D. R. Smith,, and S. B. Prusiner. 1987. Purified scrapie prions resist inactivation by procedures that hydrolyze, modify, or shear nucleic acids. Virology 160:271274.
5. Belt, P. B. G. M.,, I. H. Muileman,, B. E. C. Schreuder,, J. B. Ruijter,, A. L. J. Gielkens,, and M. A. Smits. 1995. Identification of five allelic variants of the sheep PrP gene and their association with natural scrapie. J. Gen. Virol. 76:509517.
6. Bessen, R. A.,, D. A. Kocisko,, G. J. Raymond,, S. Nandan,, P. T. LansburyJr., and B. Caughey. 1995. Non-genetic propagation of strain-specific properties of scrapie prion protein. Nature 375:698700.
7. Bolton, D. C.,, and P. E. Bendheim. 1988. A modified host protein model of scrapie. Ciba Found. Symp. 135:164181.
8. Bossers, A.,, P. B. G. M. Belt,, G. J. Raymond,, B. Caughey,, R. de Vries,, and M. A. Smits. 1997. Scrapie susceptibility-linked polymorphisms modulate the in vitro conversion of sheep prion protein to protease-resistant forms. Proc. Natl. Acad. Sci. USA 94:49314936.
9. Bots, G. T.,, J. C. Man,, and A. Verjaal. 1971. Virus-like particles in brain tissue from two patients with Creutzfeldt-Jakob disease. Acta Neuropathol. (Berlin) 18:267270.
10. Bratberg, B.,, K. Ueland,, and G. A. H. Wells. 1995. Feline spongiform encephalopathy in a cat in Norway. Vet. Rec. 136:444.
11. Brotherston, J. G.,, C. C. Renwick,, J. T. Stamp,, I. Zlotnik,, and I. H. Pattison. 1968. Spread of scrapie by contact to goats and sheep. J. Comp. Pathol. 78:917.
12. Brown, K. L.,, K. Stewart,, D. L. Ritchie,, N. A. Mabbott,, A. Williams,, H. Fraser,, W. I. Morrison,, and M. E. Bruce. 1999. Scrapie replication in lymphoid tissues depends on prion protein-expressing follicular dendritic cells. Nat. Med. 5:13081312.
13. Brown, P.,, F. Cathala,, R. F. Raubertas,, D. C. Cajdusek,, and P. Castaigne. 1987. The epidemiology of Creutzfeldt-Jakob disease: conclusion of a 15-year investigation in France and review of the world literature. Neurology 37:895904.
14. Brown, P. 1988. The clinical neurology and epidemiology of Creutzfeldt-Jakob disease, with special reference to iatrogenic cases. Ciba Found. Symp. 135:323.
15. Brown, P. 1988. Human growth hormone therapy and Creutzfeldt-Jakob disease: a drama in three acts. Pediatrics 81:8592.
16. Bruce, M. E.,, R. G. Will,, J. W. Ironside,, I. McConnell,, D. Drummond,, A. Suttie,, L. McCardle,, A. Chree,, J. Hope,, C. Birkett,, S. Cousens,, H. Fraser,, and C. J. Bostock. 1997. Transmissions to mice indicate that a new variant CJD is caused by the BSE agent. Nature 389:498501.
17. Carlson, G. A.,, D. T. Kingsbury,, P. A. Goodman,, S. Coleman,, S. T. Marshall,, S. J. DeArmond,, D. Westaway,, and S. B. Prusiner. 1986. Linkage of prion protein and scrapie incubation time genes. Cell 46:503511.
18. Caughey, B.,, K. Brown,, G. J. Raymond,, G. E. Katzenstein,, and W. Thresher. 1994. Binding of the protease-sensitive form of prion protein PrP to sulfated glycosaminoglycan and Congo red. J. Virol. 68:21352141.
19. Caughey, B.,, D. Ernst,, and R. Race. 1993. Congo red inhibition of scrapie agent replication. J. Virol 67:62706272.
20. Chabry, J.,, B. Caughey,, and B. Chesebro. 1998. Specific inhibition of in vitro formation of protease resistant prion protein by synthetic peptides. J. Biol Chem. 273:1320313207.
21. Chandler, R. L. 1961. Encephalopathy in mice produced by inoculation with scrapie brain material. Lancet i:13781379.
22. Chandler, R. L. 1962. Encephalopathy in mice. Lancet i:107108.
23. Chandler, R. L. 1963. Experimental scrapie in the mouse. Res. Vet. Sci. 4:276.
24. Cho, H. J.,, and A. S. Greig. 1975. Isolation of 14-nm virus-like particles from mouse brain infected with scrapie agent. Nature 257:685686.
25. Clouscard, C.,, P. Beaudry,, J. M. Elsen,, D. Milan,, M. Dussaucy,, C. Bounneau,, F. Schelcher,, J. Chatelain,, J. J. Launay,, and J. L. Laplanche. 1995. Different allelic effects of the codon 136 and 171 of the prion protein gene in sheep with natural scrapie. J. Gen. Virol. 76:20972101.
26. Collinge, J.,, K. C. L. Sidle,, J. Meads,, J. Ironside,, and A. F. Hill. 1996. Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 383:685690.
27. Cuille, J.,, and P. L. Chelle. 1936. La maladie dite tremblante du mouton: estelle inoculable? Acad. Sci. Paris 203:15521554.
28. Czub, M.,, H. R. Braig,, and H. Diringer. 1988. Replication of scrapie agent in hamsters infected intracerebrally confirms the pathogenesis of an amyloid-inducing virosis. J. Gen. Virol 69:17531756.
29. Dawson, M.,, G. A. H. Wells,, B. N. J. Parker,, and A. C. Scott 1990. Primary parenteral transmission of bovine spongiform encephalopathy to the pig. Vet. Rec. 127:338.
30. Dickinson, A. G.,, and G. W. Outram,. 1979. The scrapie replication-site hypothesis and its implication for pathogenesis, p. 1332. In S. B. Prusiner, and W. J. Hadlow (ed.), Slow Transmissible Diseases of the Nervous System, vol. 2. Academic Press, New York, N.Y.
31. Dickinson, A. G.,, J. T. Stamp,, and C. C. Renwick. 1974. Maternal and lateral transmission of scrapie in sheep. J. Comp. Pathol. 84:1925.
32. Duguid, J. R.,, R. G. Rohwer,, and B. Seed. 1988. Isolation of cDNAs of scrapie-modulated RNAs by subtractive hybridization of a cDNA library. Proc. Natl. Acad. Sci. USA 85:57385742.
33. Foote, W. C.,, W. Clark,, A. Maciulis,, J. W. Call,, J. Hourrigan,, C. Evans,, M. Marshall,, and M. de Camp. 1993. Prevention of scrapie transmission in sheep using embryo transfer. Am J. Vet. Res. 54:18631868.
34. Foster, J. D.,, M. Bruce,, I. McConnell,, A. Chee,, and H. Fraser. 1996. Detection of BSE infectivity in brain and spleen of experimentally infected sheep. Vet. Rec. 133:546548.
35. Foster, J. D.,, J. Hope,, and H. Fraser. 1993. Transmission of bovine spongiform encephalopathy to sheep and goats. Vet. Rec. 133:339341.
36. Foster, J. D.,, W. A. C. McKelvey,, J. A. Mylne,, A. Williams,, N. Hunter,, J. Hope,, and H. Fraser. 1992. Studies on maternal transmission of scrapie in sheep by embryo transfer. Vet. Rec. 130:341343.
37. Foster, J. D.,, N. Hunter,, A. Williams,, J. A. Mylne,, W. A. C. McKelvey,, J. Hope,, H. Fraser,, and C. Bostock. 1996. Observations on the transmission of scrapie in experiments using embryo transfer. Vet. Rec. 138:559562.
38. Fraser, H.,, I. McConnell,, G. A. H. Wells,, and M. Dawson. 1988. Transmission of bovine spongiform encephalopathy to mice. Vet. Rec. 123:472.
39. Goldmann, W.,, N. Hunter,, G. Smith,, J. Foster,, and J. Hope. 1994a. PrP genotypes and Sip gene in Cheviot sheep form the basis for scrapie strain typing in sheep. Ann. N.Y. Acad. Sci. 724:296299.
40. Goldmann, W.,, N. Hunter,, G. Smith,, J. Foster,, and J. Hope. 1994b. 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. 75:989995.
41. Hadlow, W. J.,, R. C. Kennedy,, and R. E. Race. 1982. Natural infection of Suffolk sheep with scrapie virus. J. Infect. Dis. 146:657664.
42. Harries Jones, R.,, R. Knight,, R. G. Will,, S. N. Cousens,, P. G. Smith,, and W. B. Mathews. 1988. Creutzfeldt-Jakob disease in England and Wales, 1980-1984: a case-control study of potential risk factors. J. Neurol. Neurosurg. Psychiatry 51:11131119.
43. Hartsough, G. R.,, and D. Burger. 1965. Encephalopathy of mink. I. Epizootologic and clinical observations. J. Infect. Dis. 115:387392.
44. Hedge, R. S.,, P. Tremblay,, D. Groth,, S. J. DeArmond,, S. B. Prusiner,, and V. R. Lingappa. 1999. Transmissible and genetic prion diseases share a common pathway of neurodegeneration. Nature 402:822826.
45. Hill, A. F.,, M. Desbruslais,, S. Joiner,, K. C. L. Sidle,, I. Gowland,, and J. Collinge. 1997. The same prion strain causes vCJD and BSE. Nature 389:448450.
46. Hill, A. F.,, M. Zeidler,, J. W. Ironside,, and J. Collinge. 1997. Diagnosis of new variant Creutzfeldt-Jakob disease by tonsil biopsy. Lancet 349:99100.
47. Horiuchi, M.,, and B. Caughey. 1999. Specific binding of normal prion protein to the scrapie form via a localized domain initiates its conversion to the protease-resistant state. EMBO J. 18:31933203.
48. Hourrigan, J.,, A. Klingsporn,, W. W. Clark,, and M. deCamp,. 1979. Epidemiology of scrapie in the United States, p. 331356. In S. B. Prusiner, and W. J. Hadlow (ed.), vol. 1. Slow Transmissible Diseases of the Nervous System. Academic Press, New York, N.Y.
49. Hunter, N.,, J. D. Foster,, A. G. Dickinson,, and J. Hope. 1989. Linkage of the gene for the scrapie-associated fibril protein (PrP) to the Sip gene in Cheviot sheep. Vet. Rec. 124:363366.
50. Hunter, N.,, W. Goldmann,, G. Benson,, J. D. Foster,, and J. Hope. 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. 74:10251031.
51. Hunter, N.,, W. Goldmann,, J. Foster,, D. Cairns,, and G. Smith. 1997. Natural scrapie and PrP genotype: case-control studies in British sheep. Vet. Rec. 141:137140.
52. Hunter, N.,, J. Hope,, I. McConnell,, and A. G. Dickinson. 1987. Linkage of the scrapie-associated fibril protein (PrP) gene and Sine using congenic mice and restriction fragment length polymorphism analysis. J. Gen. Virol. 68:27112716.
53. Hunter, N.,, W. Goldmann,, G. Smith,, and J. Hope. 1994. The association of a codon 136 PrP gene variant with the occurrence of natural scrapie. Arch. Virol. 137:171177.
54. Ikeda, T.,, M. Horiuchi,, N. Ishiguro,, Y. Muramatsu,, G. D. Kai-Uwe,, and M. Shinagawa. 1995. Amino acid polymorphisms of PrP with reference to the onset of scrapie in Suffolk and Corriedale sheep in Japan. J. Gen. Virol. 76:25772581.
55. Kimberlin, R. H. 1982. Scrapie agent: prions or virinos? Nature 297:107108.
56. Kimberlin, R. H.,, and C. A. Walker. 1979. Pathogenesis of mouse scrapie: dynamics of agent replication in spleen, spinal cord, and brain after infection by different routes. J. Comp. Pathol. 89:551562.
57. Kocisko, D. A.,, J. H. Come,, S. A. Priola,, B. Chesebro,, G. J. Raymond,, P. T. LansburyJr.,, and B. Caughey. 1994. Cell-free formation of protease-resistant prion protein. Nature 370:471474.
58. Kocisko, D. A.,, S. A. Priola,, G. J. Raymond,, B. Chesebro,, P. T. LansburyJr.,, and B. Caughey. 1995. Species specificity in the cell-free conversion of prion protein to protease-resistant forms: a model for the scrapie species barrier. Proc. Natl Acad. Sci. USA 92:39233927.
59. Kondo, K.,, and Y. Kuroiiwa. 1982. A case control study of Creutzfeldt-Jakob disease: association with physical injuries. Ann. Neurol. 11:377381.
60. Laplanche, J. L.,, J. Chatelain,, D. Westaway,, S. Thomas,, M. Dussaucy,, J. Brugere-Picoux,, and J. M. Launay. 1993. PrP polymorphisms associated with natural scrapie discovered by denaturing gradient gel electrophoresis. Genomics 15:3037.
61. Laplanche, J. L.,, J. Chatelain,, P. Beaudry,, M. Dussaucy,, C. Bounneau,, and J. Launay. 1993. French autochthonous scrapied sheep without the 136Val PrP polymorphism. Mamm. Genome 4:463464.
62. Lasmézas, C. I.,, J. P. Deslys,, R. Demalmay,, K. T. Adjou,, F. Lamoury,, and D. Dormont. 1996. BSE transmission to macaques. Nature 381:743744.
63. Lasmézas, C. I.,, J. P. Deslys,, O. Robain,, A. Jaegly,, V. Beringue,, J. M. Peyrin,, J. G. Fournier,, J. J. Hauw,, J. Rossier,, and D. Dormont. 1997. Transmission of the BSE agent to mice in the absence of detectable abnormal prion protein. Science 275:402405.
64. Lugaresi, E.,, R. Medori,, P. Montagna,, A. Baruzzi,, P. Cortelli,, A. Lugaresi,, P. Tinuper,, M. Zucconi,, and P. Gambetti. 1986. Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei. N. Engl. J. Med. 315:9971003.
65. Mabbott, N. A.,, K. L. Brown,, J. Manson,, and N. E. Bruce. 1997. T-lymphocyte activation and the cellular form of the prion protein. Immunology. 92:161165.
66. Maignien, T.,, C. I. Lasmezas,, V. Beringue,, D. Dormont,, and J. P. Deslys. 1999. Pathogenesis of the oral route of infection of mice with scrapie and bovine spongiform encephalopathy agents. J. Gen. Virol. 80:30353042.
67. Manson, J. C.,, E. Jamieson,, H. Baybutt,, N. L. Tuzi,, R. Barron,, I. McConnell,, R. Somerville,, J. Ironside,, R. Will,, M.S. Sy,, D. W. Melton,, J. Hope,, and C. Bostock. 1999. A single amino acid alteration (101L) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy. EMBO J. 18:68556864.
68. Manuelidis, L.,, G. Murdoch,, and E. E. Manuelidis. 1988. Potential involvement of retroviral elements in human dementias. Ciba Found. Symp. 135:117129.
69. Manuelidis, L.,, and E. E. Manuelidis. 1981. Search for specific DNAs in Creutzfeldt-Jakob infectious brain fractions using A nick translation. Virology 109:435443.
70. Marsh, R. F.,, and W. J. Hadlow. 1992. Transmissible mink encephalopathy. Rev. Sci. Tech. Off. Int. Epizoot. 11:539550.
71. McBride, P. A.,, P. Eikelenboom,, G. Kraal,, H. Fraser,, and M. E. Bruce. 1992. PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice. J. Pathol. 168:413418.
72. McKinley, M. P.,, F. R. Masiarz,, S. T. Isaacs,, J. E. Hearst,, and S. B. Prusiner. 1983. Resistance of the scrapie agent to inactivation by psoralens. Photochem. Photobiol. 37:539545.
73. Meyer, N.,, V. Rosenbaum,, B. Schmidt,, K. Gilles,, C. A. Mirenda,, D. Groth,, S. B. Prusiner,, and D. Riesner. 1991. Search for a putative scrapie genome in purified prion fractions reveals a paucity of nucleic acids. J. Gen. Virol. 72:3749.
74. Middleton, D. J.,, and R. M. Barlow. 1993. Failure to transmit bovine spongiform encephalopathy to mice by feeding them with extraneural tissues of affected cattle. Vet. Rec. 132:545547.
75. Miller, M. W.,, M. A. Wild,, and E. S. Williams. 1998. Epidemiology of chronic wasting disease in captive Rocky Mountain elk. J. Wildl. Dis. 34:532536.
76.Ministry of Agriculture,Foods and Fisheries. 1997. Bovine Spongiform Encephalopathy: an Update, June 1997. Ministry of Agriculture, Food and Fisheries, London, England.
77. Neary, K.,, B. Caughey,, D. Ernst,, R. E. Race,, and B. Chesebro. 1991. Protease sensitivity and nuclease resistance of the scrapie agent propagated in vitro in neuroblastoma cells. J. Virol. 65:10311034.
78. Oesch, B.,, D. F. Groth,, S. B. Prusiner,, and C. Weissman. 1988. Search for a scrapie-specific nucleic acid: a progress report. Ciba Found. Symp. 135:209223.
79. Onodera, T.,, T. Ikeda,, Y. Muramatsu,, and M. Shinagawa. 1993. Isolation of the scrapie agent from the placenta of sheep with natural scrapie in Japan. Microbiol. Immunol. 37:311316.
80. O’Rourke, K. I.,, R. P. Melco,, and J. R. Mickelson. 1996. Allelic frequencies of an ovine scrapie susceptibility gene. Anim. Biotechnol. 7:155162.
81. O’Rourke, K. I.,, T. V. Baszler,, S. M. Parish,, and D. P. Knowles. 1998. Preclinical detection of PrPSc in nictitating membrane lymphoid tissue of sheep. Vet. Rec. 142:489491.
82. Ozel, M.,, and H. Diringer. 1994. An extraordinarily small, suspicious, virus-like structure in fractions from scrapie hamster brain. Lancet 343:894895.
83. Parry, H. B., 1983. Recorded occurrences of scrapie from 1750, p. 3159. In D. R. Oppenheimer (ed.), Scrapie Disease in Sheep. Academic Press, New York, N.Y.
84. Parry, H. B. 1964. Natural scrapie in sheep. I. Clinical manifestation and general incidence, treatment, and related syndromes, p. 9597. In Report of the Scrapie Seminar, ARS 91-53. U.S. Department of Agriculture, Washington, D.C.
85. Pattison, I. H.,, M. N. Hoare,, J. N. Jebbett,, and W. A. Watson. 1972. Spread of scrapie to sheep and goats by oral dosing with foetal membranes from scrapie-affected sheep. Vet. Rec. 90:465468.
86. Pattison, I. H.,, M. N. Hoare,, J. N. Jebbett,, and W. A. Watson. 1974. Further observations on the production of scrapie in sheep by oral dosing with foetal membranes from scrapie-affected sheep. Br. Vet. J. 130:6567.
87. Priola, S. A.,, B. Caughey,, R. E. Race,, and B. Chesebro. 1994. Heterologous PrP molecules interfere with accumulation of protease-resistant PrP in scrapie-infected murine neuroblastoma cells. J. Virol. 68:48734878.
88. Prusiner, S. B. 1990. Transgenic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63:673686.
89. Prusiner, S. B. 1991. Molecular biology of prion disease. Science 252:15151522.
90. Prusiner, S. B. 1982. Novel proteinaceous infectious particles cause scrapie. Science 216:135144.
91. Prusiner, S. B. 1995. The prion diseases. Sci. Am. 272:4857.
92. Race, R.,, A. Jenny,, and D. Sutton. 1998. Scrapie infectivity and proteinase K-resistant prion protein in sheep placenta, brain, spleen and lymph node: implications for transmission and antemortem diagnosis. J. Infect. Dis. 178:949953.
93. Raymond, G. J.,, J. Hope,, D. A. Kocisko,, S. A. Priola,, L. D. Raymond,, A. Bossers,, J. Ironside,, R. G. Will,, S. G. Chen,, R. B. Petersen,, P. Gambetti,, R. Rubenstein,, M. A. Smits,, P. T. Lansbury, Jr., and B. Caughey. 1997. Molecular assessment of the potential transmissibilities of BSE and scrapie to humans. Nature 388:285288.
94. Robinson, M. M.,, W. J. Hadlow,, T. P. Huff,, G. A. H. Wells,, M. Dawson,, R. F. Marsh,, and J. R. Gorham. 1994. Experimental infection of mink with bovine spongiform encephalopathy. J. Gen. Virol. 75:21512155.
95. Rohwer, R. G. 1984. Scrapie infectious agent is virus-like in size and susceptibility to inactivation. Nature 308:658662.
96. Rohwer, R. G. 1984. Virus-like sensitivity of the scrapie agent to heat inactivation. Science 223:600602.
97. Schmerr, M. J.,, A. L. Jenny,, M. S. Bulgin,, J. M. Miller,, A. N. Hamir,, R. C. Cutlip,, and K. R. Goodwin. 1999. Use of capillary electrophoresis and fluorescent peptides to detect the abnormal prion protein in the blood of animals that are infected with a transmissible spongiform encephalopathy. J. Chromatogr. A 853:207-214.
98. Schreuder, B. E. C.,, L. J. M. van Keulen,, M. E. W. Viromans,, L. R M. Langeveld,, and M. A. Smits. 1996. Preclinical test for prion diseases. Nature 381:536.
99. Scott, M. R.,, D. Groth,, J. Tatzelt,, M. Torchia,, P. Tremblay,, S. J. DeArmond,, and S. B. Prusiner. 1997. Propagation of prion strains through specific conformers of the prion protein. J. Virol. 71:90329044.
100. Scott, M. R.,, R. Kohler,, D. Foster,, and S. B. Prusiner. 1992. Chimeric prion protein expression in cultured cells and transgenic mice. Protein Sci. 1:986997.
101. Scott, M. R.,, R. Will,, J. Ironside,, H.-O. B. Nguyen,, P. Tremblay,, S. J. DeArmond,, and S. B. Prusiner. 1999. Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc. Natl. Acad. Sci. USA 96:1513715142.
102. Sklaviadis, T.,, A. Akowitz,, E. E. Manuelidis,, and L. Manuelidis. 1993. Nucleic acid binding proteins in highly purified Creutzfeldt-Jakob disease preparations. Proc. Natl. Acad. Sci. USA 90:57135717.
103. Snow, A. D.,, R. Kisilevsky,, J. Willmer,, S. B. Prusiner,, and S. J. DeArmond. 1989. Sulfated glycosaminoglycans in amyloid plaques of prion diseases. Acta Neuropathol. 77:337342.
104. Spraker, T. R.,, M. W. Miller,, E. S. Williams,, D. M. Getzy,, W. J. Adrian,, G. G. Schoonveld,, R. A. Spowart,, K. I. O’Rourke,, J. M. Miller,, and P. A. Merz. 1997. Spongiform encephalopathy in free-ranging mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni) in northcentral Colorado. J. Wildl. Dis. 33:16.
105. Supattapone, S.,, H.-O. B. Nguyen,, F. E. Cohen,, S. B. Prusiner,, and M. R. Scott. 1999. Elimination of prions by branched polyamines and implications for therapeutics. Proc. Natl. Acad. Sci. USA 96:1452914534.
106. Tagliavini, F.,, R. A. McArthur,, B. Canciani,, G. Giaccone,, M. Porro,, M. Bugiani,, P. M.-J. Lievens,, O. Bugiani,, E. Peri,, P. Dall’Ara,, M. Rocchi,, G. Poli,, G. Forloni,, T. Bandiera,, M. Vasari,, A. Suarato,, P. Cassutti,, M. A. Cervini,, J. Lansen,, M. Salmona,, and C. Post. 1997. Effectiveness of anthracycline against experimental prion disease in Syrian hamsters. Science 276:11191122.
107. Tateishi, J.,, P. Brown,, T. Kitamoto,, Z. Hoque,, R. Roos,, R. Wollman,, L. Cervenakova,, and D. C. Gajdusek. 1995. First experimental transmission of fatal familial insomnia. Nature 376:434435.
108. Taylor, D. M.,, K. Fernie,, I. McConnell,, C. E. Ferguson,, and P. J. Steele. 1998. Solvent extraction as an adjunct to rendering: the effect on BSE and scrapie agents of hot solvents followed by dry heat and steam. Vet. Rec. 143:69.
109. Telling, G. C.,, M. Scott,, J. Mastrianni,, R. Gabizon,, M. Torchia,, F. E. Cohen,, S. J. DeArmond,, and S. B. Prusiner. 1995. Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell 83:7990.
110. Weissman, C. 1991. A unified theory of prion propagation. Nature 352:679683.
111. Wells, G. A. H.,, M. Dawson,, S. A. C. Hawkins,, R. B. Green,, I. Dexter,, M. F. Francis,, M. M. Simmons,, A. R. Austin,, and M. W. Horigan. 1994. Infectivity in the ileum of cattle challenged orally with bovine spongiform encephalopathy. Vet. Rec. 135:4041.
112. Wells, G. A. H.,, S. A. C. Hawkins,, R. B. Green,, A. R. Austin,, I. Dexter,, Y. I. Spencer,, M. J. Chaplin,, M. J. Stack,, and M. Dawson. 1998. Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update. Vet. Rec. 142:103106.
113. Wells, G. A. H.,, A. C. Scott,, C. T. Johnson,, R. F. Gunning,, R. D. Hancock,, M. Jeffrey,, M. Dawson,, and R. Bradley. 1987. A novel progressive spongiform encephalopathy in cattle. Vet. Rec. 121:419420.
114. Westaway, D., R A. Goodman, C. A. Mirenda, M. P. McKinley, G. A. Carlson, and S. B. Prusiner. 1987. Distinct prion proteins in short and long scrapie incubation period mice. Cell 51:651662.
115. Westaway, D.,, V. Zuliani,, C. M. Cooper,, M. DaCosta,, S. Neuman,, A. L. Jenny,, L. Detwiler,, and S. B. Prusiner. 1994. Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie. Genes Dev. 8:959969.
116. Wilesmith, J. W.,, J. B. M. Ryan,, W. D. Hueston,, and L. J. Hoinville. 1992. Bovine spongiform encephalopathy: epidemiological features 1985 to 1990. Vet. Rec. 130:9094.
117. Wilesmith, J. W.,, G. A. H. Wells,, J. B. M. Ryan,, D. Gavier-Widen,, and M. M. Simmons. 1997. A cohort study to examine maternally associated risk factors for bovine spongiform encephalopathy Vet. Rec. 141:239243.
118. Will, R. 1999. New variant Creutzfeldt-Jakob disease. Biomed. Pharmacother. 53:913.
119. Will, R. G.,, J. W. Ironside,, M. Zeidler,, S. N. Cousens,, K. Estibeiro,, A. Alperovitch,, S. Poser,, M. Pocchiari,, A. Hofman,, and P. G. Smith. 1996. Anew variant of Creutzfeldt-Jakob disease in the UK. Lancet 347:921925.
120. Williams, E. S.,, and S. Young. 1980. Chronic wasting disease of captive mule deer: a spongiform encephalopathy. J. Wildl. Dis. 16:8998.
121. Williams, E. S.,, and S. Young. 1982. Spongiform encephalopathy of Rocky Mountain elk. J. Wildl Dis. 18:465471.
122. Williams, E. S.,, and S. Young. 1992. Spongiform encephalopathies in Cervidae. Rev. Sci. Tech. Off. Int. Epizoot. 11:551567.
123. Wyatt, J. M.,, G. R. Pearson,, T. N. Smerdon,, T. J. Gruffydd-Jones,, G. A. H. Wells,, and J. W. Wilesmith. 1991. Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats. Vet. Rec. 129:233236.
124. Wyatt, J. M.,, G. R. Pearson,, T. Smerdon,, T. J. Gruffydd-Jones,, and G. A. H. Wells. 1990. Spongiform encephalopathy in a cat. Vet. Rec. 126:513.

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