DOI: 10.1126/science.278.5336.245. Prion Diseases and the BSE Crisis

10.1126/science.278.5336.245

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Bovine spongiform encephalopathy (BSE) and human Creutzfeldt-Jakob disease (CJD) are among the most notable central nervous system degenerative disorders caused by prions. CJD may present as a sporadic, genetic, or infectious illness. Prions are transmissible particles that are devoid of nucleic acid and seem to be composed exclusively of a modified protein (PrP Sc ). The normal, cellular prion protein (PrP C ) is converted into PrP Sc through a posttranslational process during which it acquires a high β-sheet content. It is thought that BSE is a result of cannibalism in which faulty industrial practices produced prion-contaminated feed for cattle. There is now considerable concern that bovine prions may have been passed to humans, resulting in a new form of CJD.

Bibliography

Prusiner, S. B. (1997). Prion Diseases and the BSE Crisis. Science, 278(5336), 245â251.

Authors 1

Stanley B. Prusiner (first)

References 177 Referenced 765

Prions are defined as proteinaceous infectious particles that lack nucleic acid. PrP C is the cellular prion protein; PrP Sc is the pathologic isoform. Amino-terminal truncation during limited proteolysis of PrP Sc produces PrP 27–30 (so named because this protease-resistant core of PrP Sc migrates at ∼27 to 30 kD).
10.1126/science.1675487
10.1073/pnas.90.23.10962
Meyer R. K., et al., ibid. 83, 2310 (1986). / ibid. by Meyer R. K. (1986)
Oesch B., et al., Cell 40, 735 (1985). (10.1016/0092-8674(85)90333-2) / Cell by Oesch B. (1985)
Bateman D., et al., Lancet 346, 1155 (1995); (10.1016/S0140-6736(95)91828-0) / Lancet by Bateman D. (1995)
; T. C. Britton S. Al-Sarraj C. Shaw T. Campbell J. Collinge ibid. p. 1155; G. Chazot et al. ibid. 347 1181 (1996); R. G. Will et al. ibid. p. 921.
10.1038/385197a0
10.1146/annurev.mi.43.100189.002021
Gerstmann J., Sträussler E., Scheinker I., Z. Neurol. 154, 736 (1936); / Z. Neurol. by Gerstmann J. (1936)
Masters C. L., et al., Ann. Neurol. 5, 177 (1978). (10.1002/ana.410050212) / Ann. Neurol. by Masters C. L. (1978)
Hsiao K., et al., Nature 338, 342 (1989). (10.1038/338342a0) / Nature by Hsiao K. (1989)
Gajdusek D. C., Science 197, 943 (1977). (10.1126/science.142303) / Science by Gajdusek D. C. (1977)
Hsiao K., et al., N. Engl. J. Med. 324, 1091 (1991). (10.1056/NEJM199104183241604) / N. Engl. J. Med. by Hsiao K. (1991)
Bobowick A. R., Brody J. A., Matthews M. R., Roos R., Gajdusek D. C., Am. J. Epidemiol. 98, 381 (1973). (10.1093/oxfordjournals.aje.a121567) / Am. J. Epidemiol. by Bobowick A. R. (1973)
R. Malmgren L. Kurland B. Mokri J. Kurtzke in Slow Transmissible Diseases of the Nervous System S. B. Prusiner and W. J. Hadlow Eds. (Academic Press New York 1979) vol. 1 pp. 93–112;
Brown P., Cathala F., Raubertas R. F., Gajdusek D. C., Castaigne P., Neurology 37, 895 (1987); (10.1212/WNL.37.6.895) / Neurology by Brown P. (1987)
Harries-Jones R., et al., J. Neurol. Neurosurg. Psychiatry 51, 1113 (1988); (10.1136/jnnp.51.9.1113) / J. Neurol. Neurosurg. Psychiatry by Harries-Jones R. (1988)
Cousens S. N., et al., ibid. 53, 459 (1990). / ibid. by Cousens S. N. (1990)
F. Meggendorfer Z. Gesamte Neurol. Psychiatr. 128 337 (1930); A. Stender ibid. p. 528; N. P. Rosenthal (10.1007/BF02864285)
Keesey J., Crandall B., Brown W. J., Arch. Neurol. 33, 252 (1976). (10.1001/archneur.1976.00500040036005) / Arch. Neurol. by Keesey J. (1976)
Masters C. L., Gajdusek D. C., Gibbs C. J., Brain 104, 559 (1981). (10.1093/brain/104.3.559) / Brain by Masters C. L. (1981)
Carlson G. A., et al., Cell 46, 503 (1986). (10.1016/0092-8674(86)90875-5) / Cell by Carlson G. A. (1986)
K. Doh-ura
Tateishi J., Sasaki H., Kitamoto T., Sakaki Y., Biochem. Biophys. Res. Commun. 163, 974 (1989); (10.1016/0006-291X(89)92317-6) / Biochem. Biophys. Res. Commun. by Tateishi J. (1989)
Goldgaber D., et al., Exp. Neurol. 106, 204 (1989); (10.1016/0014-4886(89)90095-2) / Exp. Neurol. by Goldgaber D. (1989)
Kretzschmar H. A., et al., Lancet 337, 1160 (1991). (10.1016/0140-6736(91)92826-N) / Lancet by Kretzschmar H. A. (1991)
Dlouhy S. R., et al., Nature Genet. 1, 64 (1992); (10.1038/ng0492-64) / Nature Genet. by Dlouhy S. R. (1992)
Petersen R. B., et al., Neurology 42, 1859 (1992); (10.1212/WNL.42.10.1859) / Neurology by Petersen R. B. (1992)
Poulter M., et al., Brain 115, 675 (1992); (10.1093/brain/115.3.675) / Brain by Poulter M. (1992)
Gabizon R., et al., Am. J. Hum. Genet. 53, 828 (1993). / Am. J. Hum. Genet. by Gabizon R. (1993)
Hsiao K. K., et al., Science 250, 1587 (1990). (10.1126/science.1980379) / Science by Hsiao K. K. (1990)
10.1073/pnas.91.19.9126
Telling G. C., et al., Genes Dev. 10, 1736 (1996). (10.1101/gad.10.14.1736) / Genes Dev. by Telling G. C. (1996)
Büeler H., et al., Nature 356, 577 (1992). (10.1038/356577a0) / Nature by Büeler H. (1992)
Telling G. C., et al., Cell 83, 79 (1995). (10.1016/0092-8674(95)90236-8) / Cell by Telling G. C. (1995)
10.1126/science.274.5295.2079
M. R. Scott et al. Protein Sci. 6 (suppl. 1) 84 (1997).
M. P. Alpers in The Central Nervous System Some Experimental Models of Neurological Diseases O. T. Bailey and D. E. Smith Eds. (Williams & Wilkins Baltimore 1968) pp. 234–251.
___ in Prions—Novel Infectious Pathogens Causing Scrapie and Creutzfeldt-Jakob Disease S. B. Prusiner and M. P. McKinley Eds. (Academic Press Orlando FL 1987) pp. 451–465.
Brown P., Preece M. A., Will R. G., Lancet 340, 24 (1992). (10.1016/0140-6736(92)92431-E) / Lancet by Brown P. (1992)
Billette de Villemeur T., et al., Neurology 47, 690 (1996); (10.1212/WNL.47.3.690) / Neurology by Billette de Villemeur T. (1996)
; PHS Interagency Coordinating Committee Report on Human Growth Hormone and Creutzfeldt-Jakob Disease (1997) vol. 14 pp. 1–11.
Esmonde T., Lueck C. J., Symon L., Duchen L. W., Will R. G., J. Neurol. Neurosurg. Psychiatry 56, 999 (1993); (10.1136/jnnp.56.9.999) / J. Neurol. Neurosurg. Psychiatry by Esmonde T. (1993)
Lane K. L., et al., Neurosurgery 34, 737 (1994); / Neurosurgery by Lane K. L. (1994)
; J. Tateishi and T. Kitamoto in preparation.
I. H. Pattison in Slow Latent and Temperate Virus Infections NINDB Monograph 2 D. C. Gajdusek C. J. Gibbs Jr. M. P. Alpers Eds. (U.S. Government Printing Office Washington DC 1965) pp. 249–257;
Pattison I. H., Jones K. M., Res. Vet. Sci. 9, 408 (1968). (10.1016/S0034-5288(18)34525-9) / Res. Vet. Sci. by Pattison I. H. (1968)
10.1073/pnas.94.19.10069
Scott M., et al., Cell 59, 847 (1989). (10.1016/0092-8674(89)90608-9) / Cell by Scott M. (1989)
Kimberlin R. H., Walker C. A., Fraser H., J. Gen. Virol. 70, 2017 (1989). (10.1099/0022-1317-70-8-2017) / J. Gen. Virol. by Kimberlin R. H. (1989)
Hecker R., et al., Genes Dev. 6, 1213 (1992). (10.1101/gad.6.7.1213) / Genes Dev. by Hecker R. (1992)
Telling G. C., et al., Proc. Natl. Acad. Sci. U.S.A. 91, 9936 (1994). (10.1073/pnas.91.21.9936) / Proc. Natl. Acad. Sci. U.S.A. by Telling G. C. (1994)
Borchelt D. R., Scott M., Taraboulos A., Stahl N., Prusiner S. B., J. Cell Biol. 110, 743 (1990); (10.1083/jcb.110.3.743) / J. Cell Biol. by Borchelt D. R. (1990)
10.1016/S0021-9258(18)55257-1
Gasset M., et al., Proc. Natl. Acad. Sci. U.S.A. 89, 10940 (1992). (10.1073/pnas.89.22.10940) / Proc. Natl. Acad. Sci. U.S.A. by Gasset M. (1992)
Huang Z., et al., ibid. 91, 7139 (1994). / ibid. by Huang Z. (1994)
Pergami P., Jaffe H., Safar J., Anal. Biochem. 236, 63 (1996). (10.1006/abio.1996.0132) / Anal. Biochem. by Pergami P. (1996)
Zhang H., et al., J. Mol. Biol. 250, 514 (1995). (10.1006/jmbi.1995.0395) / J. Mol. Biol. by Zhang H. (1995)
Schätzl H. M., Da Costa M., Taylor L., Cohen F. E., Prusiner S. B., ibid. 245, 362 (1995); / ibid. by Schätzl H. M. (1995)
Bamborough P., et al., Cold Spring Harbor Symp. Quant. Biol. 61, 495 (1996). (10.1101/SQB.1996.061.01.050) / Cold Spring Harbor Symp. Quant. Biol. by Bamborough P. (1996)
Scott M., et al., Cell 73, 979 (1993). (10.1016/0092-8674(93)90275-U) / Cell by Scott M. (1993)
Krakauer D. C., Pagel M., Southwood T. R. E., Zanotto P. M., Nature 380, 675 (1996). (10.1038/380675a0) / Nature by Krakauer D. C. (1996)
10.1021/bi952965e
Zhang H., et al., ibid. 36, 3543 (1997). / ibid. by Zhang H. (1997)
T. L. James et al. Proc. Natl. Acad. Sci. U.S.A. 94 10086 (1997).
10.1038/382180a0
M. Billeter et al. Proc. Natl. Acad. Sci. U.S.A. 94 7281 (1997). (10.1073/pnas.94.14.7281)
Riek R., Hornemann S., Wider G., Glockshuber R., Wüthrich K., FEBS Lett. 413, 282 (1997). (10.1016/S0014-5793(97)00920-4) / FEBS Lett. by Riek R. (1997)
D. G. Donne et al. Proc. Natl. Acad. Sci. U.S.A. in press. The consensus sequence of octarepeats in the NH 2 -terminal region is [P(Q/H)GGG(G/−)- WGQ].
Z. Huang S. B. Prusiner F. E. Cohen Folding Design 1 13 (1996). (10.1016/S1359-0278(96)00007-7)
Turk E., Teplow D. B., Hood L. E., Prusiner S. B., Eur. J. Biochem. 176, 21 (1988). (10.1111/j.1432-1033.1988.tb14246.x) / Eur. J. Biochem. by Turk E. (1988)
Muramoto T., Scott M., Cohen F., Prusiner S. B., Proc. Natl. Acad. Sci. U.S.A. 93, 15457 (1996). (10.1073/pnas.93.26.15457) / Proc. Natl. Acad. Sci. U.S.A. by Muramoto T. (1996)
Prusiner S. B., et al., Cell 35, 349 (1983). (10.1016/0092-8674(83)90168-X) / Cell by Prusiner S. B. (1983)
Caughey B. W., et al., Biochemistry 30, 7672 (1991); (10.1021/bi00245a003) / Biochemistry by Caughey B. W. (1991)
Gasset M., Baldwin M. A., Fletterick R. J., Prusiner S. B., Proc. Natl. Acad. Sci. U.S.A. 90, 1 (1993); (10.1073/pnas.90.1.1) / Proc. Natl. Acad. Sci. U.S.A. by Gasset M. (1993)
Safar J., Roller P. P., Gajdusek D. C., Gibbs C. J., J. Biol. Chem. 268, 20276 (1993). (10.1016/S0021-9258(20)80725-X) / J. Biol. Chem. by Safar J. (1993)
Rogers M., Yehiely F., Scott M., Prusiner S. B., Proc. Natl. Acad. Sci. U.S.A. 90, 3182 (1993). (10.1073/pnas.90.8.3182) / Proc. Natl. Acad. Sci. U.S.A. by Rogers M. (1993)
Fischer M., et al., EMBO J. 15, 1255 (1996). (10.1002/j.1460-2075.1996.tb00467.x) / EMBO J. by Fischer M. (1996)
D. Peretz et al. J. Mol. Biol. in press.
Dickinson A. G., Meikle V. M. H., Fraser H., J. Comp. Pathol. 78, 293 (1968). (10.1016/0021-9975(68)90005-4) / J. Comp. Pathol. by Dickinson A. G. (1968)
Kimberlin R. H., Trends Biochem. Sci. 7, 392 (1982); (10.1016/0968-0004(82)90182-7) / Trends Biochem. Sci. by Kimberlin R. H. (1982)
; A. G. Dickinson and G. W. Outram in Novel Infectious Agents and the Central Nervous System vol. 135 of Ciba Foundation Symposium G. Bock and J. Marsh Eds. (Wiley Chichester UK 1988);
Kimberlin R. H., Semin. Virol. 1, 153 (1990); / Semin. Virol. by Kimberlin R. H. (1990)
Bruce M. E., McConnell I., Fraser H., Dickinson A. G., J. Gen. Virol. 72, 595 (1991); (10.1099/0022-1317-72-3-595) / J. Gen. Virol. by Bruce M. E. (1991)
Weissmann C., Nature 352, 679 (1991); (10.1038/352679a0) / Nature by Weissmann C. (1991)
Ridley R. M., Baker H. F., Neurodegeneration 5, 219 (1996). (10.1006/neur.1996.0030) / Neurodegeneration by Ridley R. M. (1996)
Dickinson A. G., Meikle V. M., Genet. Res. 13, 213 (1969); (10.1017/S0016672300002895) / Genet. Res. by Dickinson A. G. (1969)
Bruce M. E., Dickinson A. G., J. Gen. Virol. 68, 79 (1987). (10.1099/0022-1317-68-1-79) / J. Gen. Virol. by Bruce M. E. (1987)
Bruce M., et al., Philos. Trans. R. Soc. London Ser. B 343, 405 (1994). (10.1098/rstb.1994.0036) / Philos. Trans. R. Soc. London Ser. B by Bruce M. (1994)
Westaway D., et al., Cell 51, 651 (1987); (10.1016/0092-8674(87)90134-6) / Cell by Westaway D. (1987)
Carlson G. A., et al., Mol. Cell. Biol. 8, 5528 (1988); / Mol. Cell. Biol. by Carlson G. A. (1988)
Carlson G. A., et al., Proc. Natl. Acad. Sci. U.S.A. 91, 5690 (1994). (10.1073/pnas.91.12.5690) / Proc. Natl. Acad. Sci. U.S.A. by Carlson G. A. (1994)
Fraser H., Dickinson A. G., J. Comp. Pathol. 78, 301 (1968). (10.1016/0021-9975(68)90006-6) / J. Comp. Pathol. by Fraser H. (1968)
Carp R. I., Meeker H., Sersen E., J. Gen. Virol. 78, 283 (1997). (10.1099/0022-1317-78-1-283) / J. Gen. Virol. by Carp R. I. (1997)
Bessen R. A., Marsh R. F., ibid. 73, 329 (1992); / ibid. by Bessen R. A. (1992)
; J. Virol. 68 7859 (1994); (10.1128/jvi.68.12.7859-7868.1994)
10.1038/375698a0
M. Scott et al. J. Virol. in press.
Monari L., et al., Proc. Natl. Acad. Sci. U.S.A. 91, 2839 (1994). (10.1073/pnas.91.7.2839) / Proc. Natl. Acad. Sci. U.S.A. by Monari L. (1994)
Parchi P., et al., Ann. Neurol. 39, 767 (1996). (10.1002/ana.410390613) / Ann. Neurol. by Parchi P. (1996)
10.1038/382779a0
Stekel D. J., Nowak M. A., Southwood T. R. E., ibid. 381, 119 (1996). / ibid. by Stekel D. J. (1996)
Wilesmith J. W., Ryan J. B. M., Atkinson M. J., Vet. Rec. 128, 199 (1991). (10.1136/vr.128.9.199) / Vet. Rec. by Wilesmith J. W. (1991)
Wilesmith J. W., Semin. Virol. 2, 239 (1991); / Semin. Virol. by Wilesmith J. W. (1991)
; R. H. Kimberlin in Bovine Spongiform Encephalopathy: The BSE Dilemma C. J. Gibbs Jr. Ed. (Springer New York 1996) pp. 155–175. (10.1007/978-1-4612-2406-8_13)
W. Goldmann N. Hunter J. Manson J. Hope Proceedings of the VIIIth International Congress of Virology Berlin 26 to 31 August 1990 p. 284;
Goldmann W., Hunter N., Martin T., Dawson M., Hope J., J. Gen. Virol. 72, 201 (1991). (10.1099/0022-1317-72-1-201) / J. Gen. Virol. by Goldmann W. (1991)
Prusiner S. B., et al., J. Infect. Dis. 167, 602 (1993). (10.1093/infdis/167.3.602) / J. Infect. Dis. by Prusiner S. B. (1993)
Hunter N., Goldmann W., Smith G., Hope J., Vet. Rec. 135, 400 (1994). (10.1136/vr.135.17.400) / Vet. Rec. by Hunter N. (1994)
Fraser H., McConnell I., Wells G. A. H., Dawson M., ibid. 123, 472 (1988); / ibid. by Fraser H. (1988)
; M. Dawson G. A. H. Wells B. N. J. Parker ibid. 126 112 (1990); ___ and A. C. Scott ibid. 127 338 (1990); M. Bruce A. Chree I. McConnell J. Foster H. Fraser in Proceedings of the IXth International Congress of Virology Glasgow Scotland 1993 p. 93.
Robinson M. M., et al., J. Comp. Pathol. 113, 241 (1995). (10.1016/S0021-9975(05)80039-8) / J. Comp. Pathol. by Robinson M. M. (1995)
J. Wilesmith unpublished data.
Hsich G., Kenney K., Gibbs C. J., Lee K. H., Harrington M. G., N. Engl. J. Med. 335, 924 (1996). (10.1056/NEJM199609263351303) / N. Engl. J. Med. by Hsich G. (1996)
Hope J., et al., Nature 336, 390 (1988); (10.1038/336390a0) / Nature by Hope J. (1988)
Serban D., Taraboulos A., DeArmond S. J., Prusiner S. B., Neurology 40, 110 (1990); (10.1212/WNL.40.1.110) / Neurology by Serban D. (1990)
Taraboulos A., et al., Proc. Natl. Acad. Sci. U.S.A. 89, 7620 (1992); (10.1073/pnas.89.16.7620) / Proc. Natl. Acad. Sci. U.S.A. by Taraboulos A. (1992)
Grathwohl K.-U. D., Horiuchi M., Ishiguro N., Shinagawa M., J. Virol. Methods 64, 205 (1997). (10.1016/S0166-0934(97)02197-6) / J. Virol. Methods by Grathwohl K.-U. D. (1997)
Taylor K. C., Vet. Rec. 129, 522 (1991); / Vet. Rec. by Taylor K. C. (1991)
. ID median infective dose.
Fraser H., Bruce M. E., Chree A., McConnell I., Wells G. A. H., J. Gen. Virol. 73, 1891 (1992). (10.1099/0022-1317-73-8-1891) / J. Gen. Virol. by Fraser H. (1992)
10.1126/science.275.5298.402
Hunter G. D., Millson G. C., Chandler R. L., Res. Vet. Sci. 4, 543 (1963); (10.1016/S0034-5288(18)34840-9) / Res. Vet. Sci. by Hunter G. D. (1963)
Eklund C. M., Kennedy R. C., Hadlow W. J., J. Infect. Dis. 117, 15 (1967); (10.1093/infdis/117.1.15) / J. Infect. Dis. by Eklund C. M. (1967)
10.1099/0022-1317-34-2-295
Prusiner S. B., et al., Ann. Neurol. 11, 353 (1982). (10.1002/ana.410110406) / Ann. Neurol. by Prusiner S. B. (1982)
U.S. Centers for Disease Control and Prevention Morb. Mortal. Wkly. Rep. 45 665 (1996)
J. W. Ironside Amyloid Int. J. Exp. Clin. Invest. 4 66 (1997). (10.3109/13506129708995272)
Baker H. F., Ridley R. M., Wells G. A. H., Vet. Rec. 132, 403 (1993). (10.1136/vr.132.16.403) / Vet. Rec. by Baker H. F. (1993)
Lasmézas C. I., et al., Nature 381, 743 (1996); (10.1038/381743a0) / Nature by Lasmézas C. I. (1996)
; R. Ridley and H. Baker unpublished data.
Hadlow W. J., Kennedy R. C., Race R. E., J. Infect. Dis. 146, 657 (1982). (10.1093/infdis/146.5.657) / J. Infect. Dis. by Hadlow W. J. (1982)
J. Collinge et al. Nature 378 779 (1995). (10.1038/378779a0)
G. J. Raymond et al. ibid. 388 285 (1997). (10.1038/40876)
Collinge J., Sidle K. C. L., Meads J., Ironside J., Hill A. F., ibid. 383, 685 (1996). / ibid. by Collinge J. (1996)
P. Parchi et al. ibid. 386 232 (1997); R. A. Somerville et al. ibid. p. 564.
Haraguchi T., et al., Arch. Biochem. Biophys. 274, 1 (1989); (10.1016/0003-9861(89)90409-8) / Arch. Biochem. Biophys. by Haraguchi T. (1989)
Endo T., Groth D., Prusiner S. B., Kobata A., Biochemistry 28, 8380 (1989). (10.1021/bi00447a017) / Biochemistry by Endo T. (1989)
Hornabrook R. W., Brain 91, 53 (1968); (10.1093/brain/91.1.53) / Brain by Hornabrook R. W. (1968)
Prusiner S. B., Gajdusek D. C., Alpers M. P., Ann. Neurol. 12, 1 (1982); (10.1002/ana.410120102) / Ann. Neurol. by Prusiner S. B. (1982)
; P. Brown in Developments in Biological Standardization F. Brown Ed. (Karger Basel Switzerland 1993) vol. 80 pp. 91–101.
R. M. Glasse Trans. N.Y. Acad. Sci. Ser. 2 29 748 (1967); (10.1111/j.2164-0947.1967.tb02298.x)
Mathews J. D., Glasse R., Lindenbaum S., Lancet ii, 449 (1968). (10.1016/S0140-6736(68)90482-0) / Lancet by Mathews J. D. (1968)
Chapman J., Ben-Israel J., Goldhammer Y., Korczyn A. D., Neurology 44, 1683 (1994); (10.1212/WNL.44.9.1683) / Neurology by Chapman J. (1994)
Spudich S., et al., Mol. Med. 1, 607 (1995). (10.1007/BF03401601) / Mol. Med. by Spudich S. (1995)
10.1126/science.7909169
Gorodinsky A., Harris D. A., J. Cell Biol. 129, 619 (1995); (10.1083/jcb.129.3.619) / J. Cell Biol. by Gorodinsky A. (1995)
; A. Taraboulos et al. ibid. p. 121; M. Vey et al. Proc. Natl. Acad. Sci. U.S.A. 93 14945 (1996); K. Kaneko et al. ibid. 94 2333 (1997);
Naslavsky N., Stein R., Yanai A., Friedlander G., Taraboulos A., J. Biol. Chem. 272, 6324 (1997). (10.1074/jbc.272.10.6324) / J. Biol. Chem. by Naslavsky N. (1997)
Hunter N., Goldmann W., Benson G., Foster J. D., Hope J., J. Gen. Virol. 74, 1025 (1993); (10.1099/0022-1317-74-6-1025) / J. Gen. Virol. by Hunter N. (1993)
Goldmann W., Hunter N., Smith G., Foster J., Hope J., ibid. 75, 989 (1994); / ibid. by Goldmann W. (1994)
Westaway D., et al., Genes Dev. 8, 959 (1994); (10.1101/gad.8.8.959) / Genes Dev. by Westaway D. (1994)
Belt P. B. G. M., et al., J. Gen. Virol. 76, 509 (1995); (10.1099/0022-1317-76-3-509) / J. Gen. Virol. by Belt P. B. G. M. (1995)
; C. Clousard et al. ibid. p. 2097; T. Ikeda et al. ibid. p. 2577;
Hunter N., Moore L., Hosie B. D., Dingwall W. S., Greig A., Vet. Rec. 140, 59 (1997); (10.1136/vr.140.3.59) / Vet. Rec. by Hunter N. (1997)
Hunter N., et al., Nature 386, 137 (1997); (10.1038/386137a0) / Nature by Hunter N. (1997)
; K. I. O'Rourke et al. J. Gen. Virol. 78 975 (1997).
Parry H. B., Heredity 17, 75 (1962); (10.1038/hdy.1962.4) / Heredity by Parry H. B. (1962)
; in Scrapie Disease in Sheep D. R. Oppenheimer Ed. (Academic Press New York 1983) pp. 31–59.
10.1016/0092-8674(93)90360-3
Prusiner S. B., et al., Proc. Natl. Acad. Sci. U.S.A. 90, 10608 (1993). (10.1073/pnas.90.22.10608) / Proc. Natl. Acad. Sci. U.S.A. by Prusiner S. B. (1993)
Collinge J., et al., Nature 370, 295 (1994); (10.1038/370295a0) / Nature by Collinge J. (1994)
Lledo P.-M., Tremblay P., DeArmond S. J., Prusiner S. B., Nicoll R. A., Proc. Natl. Acad. Sci. U.S.A. 93, 2403 (1996); (10.1073/pnas.93.6.2403) / Proc. Natl. Acad. Sci. U.S.A. by Lledo P.-M. (1996)
Sakaguchi S., et al., Nature 380, 528 (1996); (10.1038/380528a0) / Nature by Sakaguchi S. (1996)
; I. Tobler et al. ibid. p. 639.
10.1126/science.7909170
Chernoff Y. O., Lindquist S. L., Ono B.-i., Inge-Vechtomov S. G., Liebman S. W., ibid. 268, 880 (1995) ; / ibid. by Chernoff Y. O. (1995)
Derkatch I. L., Chernoff Y. O., Kushnirov V. V., Inge-Vechtomov S. G., Liebman S. W., Genetics 144, 1375 (1996); (10.1093/genetics/144.4.1375) / Genetics by Derkatch I. L. (1996)
10.1016/S0092-8674(00)80264-0
Coustou V., Deleu C., Saupe S., Begueret J., Proc. Natl. Acad. Sci. U.S.A. 94, 9773 (1997). (10.1073/pnas.94.18.9773) / Proc. Natl. Acad. Sci. U.S.A. by Coustou V. (1997)
C.-Y. King et al. Proc. Natl. Acad. Sci. U.S.A. 94 6618 (1997). (10.1073/pnas.94.13.6618)
10.1126/science.277.5324.381
Prusiner S. B., et al., Cell 63, 673 (1990); (10.1016/0092-8674(90)90134-Z) / Cell by Prusiner S. B. (1990)
; D. Groth and S. B. Prusiner unpublished data.
G. Telling et al. in preparation.
I thank F. E. Cohen and S. J. DeArmond for many stimulating discussions and their help in preparing this manuscript. Human specimens were kindly provided by J. Ironside R. Will and J. Bell. Supported by grants from NIH (NS14069 AG08967 P41-RR01081 AG02132 and NS22786) the International Human Frontiers of Science Program and the American Health Assistance Foundation as well as by gifts from the Sherman Fairchild Foundation the G. Harold and Leila Y. Mathers Foundation the Bernard Osher Foundation and Centeon Inc.

Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 5:44 a.m.)
Deposited	1 year, 7 months ago (Jan. 12, 2024, 11:50 p.m.)
Indexed	3 days, 17 hours ago (Aug. 29, 2025, 6:12 a.m.)
Issued	27 years, 10 months ago (Oct. 10, 1997)
Published	27 years, 10 months ago (Oct. 10, 1997)
Published Print	27 years, 10 months ago (Oct. 10, 1997)

Funders 0

None

BibTeX

@article{Prusiner_1997, title={Prion Diseases and the BSE Crisis}, volume={278}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.278.5336.245}, DOI={10.1126/science.278.5336.245}, number={5336}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Prusiner, Stanley B.}, year={1997}, month=oct, pages={245–251} }

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  "abstract": "<jats:p>\n            Bovine spongiform encephalopathy (BSE) and human Creutzfeldt-Jakob disease (CJD) are among the most notable central nervous system degenerative disorders caused by prions. CJD may present as a sporadic, genetic, or infectious illness. Prions are transmissible particles that are devoid of nucleic acid and seem to be composed exclusively of a modified protein (PrP\n            <jats:sup>Sc</jats:sup>\n            ). The normal, cellular prion protein (PrP\n            <jats:sup>C</jats:sup>\n            ) is converted into PrP\n            <jats:sup>Sc</jats:sup>\n            through a posttranslational process during which it acquires a high \u03b2-sheet content. It is thought that BSE is a result of cannibalism in which faulty industrial practices produced prion-contaminated feed for cattle. There is now considerable concern that bovine prions may have been passed to humans, resulting in a new form of CJD.\n          </jats:p>",
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      "unstructured": "Prions are defined as proteinaceous infectious particles that lack nucleic acid. PrP C is the cellular prion protein; PrP Sc is the pathologic isoform. Amino-terminal truncation during limited proteolysis of PrP Sc produces PrP 27\u201330 (so named because this protease-resistant core of PrP Sc migrates at \u223c27 to 30 kD)."
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      "DOI": "10.1073/pnas.90.23.10962"
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    {
      "key": "e_1_3_1_5_2",
      "first-page": "2310",
      "volume": "83",
      "author": "Meyer R. K.",
      "year": "1986",
      "unstructured": "Meyer R. K., et al., ibid. 83, 2310 (1986).",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_6_2",
      "doi-asserted-by": "crossref",
      "first-page": "735",
      "DOI": "10.1016/0092-8674(85)90333-2",
      "volume": "40",
      "author": "Oesch B.",
      "year": "1985",
      "unstructured": "Oesch B., et al., Cell 40, 735 (1985).",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_1_7_2",
      "doi-asserted-by": "crossref",
      "first-page": "1155",
      "DOI": "10.1016/S0140-6736(95)91828-0",
      "volume": "346",
      "author": "Bateman D.",
      "year": "1995",
      "unstructured": "Bateman D., et al., Lancet 346, 1155 (1995);",
      "journal-title": "Lancet"
    },
    {
      "key": "e_1_3_1_7_3",
      "unstructured": "; T. C. Britton S. Al-Sarraj C. Shaw T. Campbell J. Collinge ibid. p. 1155; G. Chazot et al. ibid. 347 1181 (1996); R. G. Will et al. ibid. p. 921."
    },
    {
      "key": "e_1_3_1_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/385197a0"
    },
    {
      "key": "e_1_3_1_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.mi.43.100189.002021"
    },
    {
      "key": "e_1_3_1_10_2",
      "first-page": "736",
      "volume": "154",
      "author": "Gerstmann J.",
      "year": "1936",
      "unstructured": "Gerstmann J., Str\u00e4ussler E., Scheinker I., Z. Neurol. 154, 736 (1936);",
      "journal-title": "Z. Neurol."
    },
    {
      "key": "e_1_3_1_10_3",
      "doi-asserted-by": "crossref",
      "first-page": "177",
      "DOI": "10.1002/ana.410050212",
      "volume": "5",
      "author": "Masters C. L.",
      "year": "1978",
      "unstructured": "Masters C. L., et al., Ann. Neurol. 5, 177 (1978).",
      "journal-title": "Ann. Neurol."
    },
    {
      "key": "e_1_3_1_11_2",
      "doi-asserted-by": "crossref",
      "first-page": "342",
      "DOI": "10.1038/338342a0",
      "volume": "338",
      "author": "Hsiao K.",
      "year": "1989",
      "unstructured": "Hsiao K., et al., Nature 338, 342 (1989).",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_12_2",
      "doi-asserted-by": "crossref",
      "first-page": "943",
      "DOI": "10.1126/science.142303",
      "volume": "197",
      "author": "Gajdusek D. C.",
      "year": "1977",
      "unstructured": "Gajdusek D. C., Science 197, 943 (1977).",
      "journal-title": "Science"
    },
    {
      "key": "e_1_3_1_13_2",
      "doi-asserted-by": "crossref",
      "first-page": "1091",
      "DOI": "10.1056/NEJM199104183241604",
      "volume": "324",
      "author": "Hsiao K.",
      "year": "1991",
      "unstructured": "Hsiao K., et al., N. Engl. J. Med. 324, 1091 (1991).",
      "journal-title": "N. Engl. J. Med."
    },
    {
      "key": "e_1_3_1_14_2",
      "doi-asserted-by": "crossref",
      "first-page": "381",
      "DOI": "10.1093/oxfordjournals.aje.a121567",
      "volume": "98",
      "author": "Bobowick A. R.",
      "year": "1973",
      "unstructured": "Bobowick A. R., Brody J. A., Matthews M. R., Roos R., Gajdusek D. C., Am. J. Epidemiol. 98, 381 (1973).",
      "journal-title": "Am. J. Epidemiol."
    },
    {
      "key": "e_1_3_1_15_2",
      "unstructured": "R. Malmgren L. Kurland B. Mokri J. Kurtzke in Slow Transmissible Diseases of the Nervous System S. B. Prusiner and W. J. Hadlow Eds. (Academic Press New York 1979) vol. 1 pp. 93\u2013112;"
    },
    {
      "key": "e_1_3_1_15_3",
      "doi-asserted-by": "crossref",
      "first-page": "895",
      "DOI": "10.1212/WNL.37.6.895",
      "volume": "37",
      "author": "Brown P.",
      "year": "1987",
      "unstructured": "Brown P., Cathala F., Raubertas R. F., Gajdusek D. C., Castaigne P., Neurology 37, 895 (1987);",
      "journal-title": "Neurology"
    },
    {
      "key": "e_1_3_1_15_4",
      "doi-asserted-by": "crossref",
      "first-page": "1113",
      "DOI": "10.1136/jnnp.51.9.1113",
      "volume": "51",
      "author": "Harries-Jones R.",
      "year": "1988",
      "unstructured": "Harries-Jones R., et al., J. Neurol. Neurosurg. Psychiatry 51, 1113 (1988);",
      "journal-title": "J. Neurol. Neurosurg. Psychiatry"
    },
    {
      "key": "e_1_3_1_15_5",
      "first-page": "459",
      "volume": "53",
      "author": "Cousens S. N.",
      "year": "1990",
      "unstructured": "Cousens S. N., et al., ibid. 53, 459 (1990).",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_16_2",
      "doi-asserted-by": "crossref",
      "unstructured": "F. Meggendorfer Z. Gesamte Neurol. Psychiatr. 128 337 (1930); A. Stender ibid. p. 528; N. P. Rosenthal",
      "DOI": "10.1007/BF02864285"
    },
    {
      "key": "e_1_3_1_16_3",
      "doi-asserted-by": "crossref",
      "first-page": "252",
      "DOI": "10.1001/archneur.1976.00500040036005",
      "volume": "33",
      "author": "Keesey J.",
      "year": "1976",
      "unstructured": "Keesey J., Crandall B., Brown W. J., Arch. Neurol. 33, 252 (1976).",
      "journal-title": "Arch. Neurol."
    },
    {
      "key": "e_1_3_1_17_2",
      "doi-asserted-by": "crossref",
      "first-page": "559",
      "DOI": "10.1093/brain/104.3.559",
      "volume": "104",
      "author": "Masters C. L.",
      "year": "1981",
      "unstructured": "Masters C. L., Gajdusek D. C., Gibbs C. J., Brain 104, 559 (1981).",
      "journal-title": "Brain"
    },
    {
      "key": "e_1_3_1_18_2",
      "doi-asserted-by": "crossref",
      "first-page": "503",
      "DOI": "10.1016/0092-8674(86)90875-5",
      "volume": "46",
      "author": "Carlson G. A.",
      "year": "1986",
      "unstructured": "Carlson G. A., et al., Cell 46, 503 (1986).",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_1_19_2",
      "unstructured": "K. Doh-ura"
    },
    {
      "key": "e_1_3_1_19_3",
      "doi-asserted-by": "crossref",
      "first-page": "974",
      "DOI": "10.1016/0006-291X(89)92317-6",
      "volume": "163",
      "author": "Tateishi J.",
      "year": "1989",
      "unstructured": "Tateishi J., Sasaki H., Kitamoto T., Sakaki Y., Biochem. Biophys. Res. Commun. 163, 974 (1989);",
      "journal-title": "Biochem. Biophys. Res. Commun."
    },
    {
      "key": "e_1_3_1_19_4",
      "doi-asserted-by": "crossref",
      "first-page": "204",
      "DOI": "10.1016/0014-4886(89)90095-2",
      "volume": "106",
      "author": "Goldgaber D.",
      "year": "1989",
      "unstructured": "Goldgaber D., et al., Exp. Neurol. 106, 204 (1989);",
      "journal-title": "Exp. Neurol."
    },
    {
      "key": "e_1_3_1_19_5",
      "doi-asserted-by": "crossref",
      "first-page": "1160",
      "DOI": "10.1016/0140-6736(91)92826-N",
      "volume": "337",
      "author": "Kretzschmar H. A.",
      "year": "1991",
      "unstructured": "Kretzschmar H. A., et al., Lancet 337, 1160 (1991).",
      "journal-title": "Lancet"
    },
    {
      "key": "e_1_3_1_20_2",
      "doi-asserted-by": "crossref",
      "first-page": "64",
      "DOI": "10.1038/ng0492-64",
      "volume": "1",
      "author": "Dlouhy S. R.",
      "year": "1992",
      "unstructured": "Dlouhy S. R., et al., Nature Genet. 1, 64 (1992);",
      "journal-title": "Nature Genet."
    },
    {
      "key": "e_1_3_1_20_3",
      "doi-asserted-by": "crossref",
      "first-page": "1859",
      "DOI": "10.1212/WNL.42.10.1859",
      "volume": "42",
      "author": "Petersen R. B.",
      "year": "1992",
      "unstructured": "Petersen R. B., et al., Neurology 42, 1859 (1992);",
      "journal-title": "Neurology"
    },
    {
      "key": "e_1_3_1_20_4",
      "doi-asserted-by": "crossref",
      "first-page": "675",
      "DOI": "10.1093/brain/115.3.675",
      "volume": "115",
      "author": "Poulter M.",
      "year": "1992",
      "unstructured": "Poulter M., et al., Brain 115, 675 (1992);",
      "journal-title": "Brain"
    },
    {
      "key": "e_1_3_1_20_5",
      "first-page": "828",
      "volume": "53",
      "author": "Gabizon R.",
      "year": "1993",
      "unstructured": "Gabizon R., et al., Am. J. Hum. Genet. 53, 828 (1993).",
      "journal-title": "Am. J. Hum. Genet."
    },
    {
      "key": "e_1_3_1_21_2",
      "doi-asserted-by": "crossref",
      "first-page": "1587",
      "DOI": "10.1126/science.1980379",
      "volume": "250",
      "author": "Hsiao K. K.",
      "year": "1990",
      "unstructured": "Hsiao K. K., et al., Science 250, 1587 (1990).",
      "journal-title": "Science"
    },
    {
      "key": "e_1_3_1_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.91.19.9126"
    },
    {
      "key": "e_1_3_1_22_3",
      "doi-asserted-by": "crossref",
      "first-page": "1736",
      "DOI": "10.1101/gad.10.14.1736",
      "volume": "10",
      "author": "Telling G. C.",
      "year": "1996",
      "unstructured": "Telling G. C., et al., Genes Dev. 10, 1736 (1996).",
      "journal-title": "Genes Dev."
    },
    {
      "key": "e_1_3_1_23_2",
      "doi-asserted-by": "crossref",
      "first-page": "577",
      "DOI": "10.1038/356577a0",
      "volume": "356",
      "author": "B\u00fceler H.",
      "year": "1992",
      "unstructured": "B\u00fceler H., et al., Nature 356, 577 (1992).",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_24_2",
      "doi-asserted-by": "crossref",
      "first-page": "79",
      "DOI": "10.1016/0092-8674(95)90236-8",
      "volume": "83",
      "author": "Telling G. C.",
      "year": "1995",
      "unstructured": "Telling G. C., et al., Cell 83, 79 (1995).",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_1_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.274.5295.2079"
    },
    {
      "key": "e_1_3_1_26_2",
      "unstructured": "M. R. Scott et al. Protein Sci. 6 (suppl. 1) 84 (1997)."
    },
    {
      "key": "e_1_3_1_27_2",
      "unstructured": "M. P. Alpers in The Central Nervous System Some Experimental Models of Neurological Diseases O. T. Bailey and D. E. Smith Eds. (Williams & Wilkins Baltimore 1968) pp. 234\u2013251."
    },
    {
      "key": "e_1_3_1_28_2",
      "unstructured": "___ in Prions\u2014Novel Infectious Pathogens Causing Scrapie and Creutzfeldt-Jakob Disease S. B. Prusiner and M. P. McKinley Eds. (Academic Press Orlando FL 1987) pp. 451\u2013465."
    },
    {
      "key": "e_1_3_1_29_2",
      "doi-asserted-by": "crossref",
      "first-page": "24",
      "DOI": "10.1016/0140-6736(92)92431-E",
      "volume": "340",
      "author": "Brown P.",
      "year": "1992",
      "unstructured": "Brown P., Preece M. A., Will R. G., Lancet 340, 24 (1992).",
      "journal-title": "Lancet"
    },
    {
      "key": "e_1_3_1_30_2",
      "doi-asserted-by": "crossref",
      "first-page": "690",
      "DOI": "10.1212/WNL.47.3.690",
      "volume": "47",
      "author": "Billette de Villemeur T.",
      "year": "1996",
      "unstructured": "Billette de Villemeur T., et al., Neurology 47, 690 (1996);",
      "journal-title": "Neurology"
    },
    {
      "key": "e_1_3_1_30_3",
      "unstructured": "; PHS Interagency Coordinating Committee Report on Human Growth Hormone and Creutzfeldt-Jakob Disease (1997) vol. 14 pp. 1\u201311."
    },
    {
      "key": "e_1_3_1_31_2",
      "doi-asserted-by": "crossref",
      "first-page": "999",
      "DOI": "10.1136/jnnp.56.9.999",
      "volume": "56",
      "author": "Esmonde T.",
      "year": "1993",
      "unstructured": "Esmonde T., Lueck C. J., Symon L., Duchen L. W., Will R. G., J. Neurol. Neurosurg. Psychiatry 56, 999 (1993);",
      "journal-title": "J. Neurol. Neurosurg. Psychiatry"
    },
    {
      "key": "e_1_3_1_31_3",
      "first-page": "737",
      "volume": "34",
      "author": "Lane K. L.",
      "year": "1994",
      "unstructured": "Lane K. L., et al., Neurosurgery 34, 737 (1994);",
      "journal-title": "Neurosurgery"
    },
    {
      "key": "e_1_3_1_31_4",
      "unstructured": "; J. Tateishi and T. Kitamoto in preparation."
    },
    {
      "key": "e_1_3_1_32_2",
      "unstructured": "I. H. Pattison in Slow Latent and Temperate Virus Infections NINDB Monograph 2 D. C. Gajdusek C. J. Gibbs Jr. M. P. Alpers Eds. (U.S. Government Printing Office Washington DC 1965) pp. 249\u2013257;"
    },
    {
      "key": "e_1_3_1_32_3",
      "doi-asserted-by": "crossref",
      "first-page": "408",
      "DOI": "10.1016/S0034-5288(18)34525-9",
      "volume": "9",
      "author": "Pattison I. H.",
      "year": "1968",
      "unstructured": "Pattison I. H., Jones K. M., Res. Vet. Sci. 9, 408 (1968).",
      "journal-title": "Res. Vet. Sci."
    },
    {
      "key": "e_1_3_1_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.94.19.10069"
    },
    {
      "key": "e_1_3_1_34_2",
      "doi-asserted-by": "crossref",
      "first-page": "847",
      "DOI": "10.1016/0092-8674(89)90608-9",
      "volume": "59",
      "author": "Scott M.",
      "year": "1989",
      "unstructured": "Scott M., et al., Cell 59, 847 (1989).",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_1_35_2",
      "doi-asserted-by": "crossref",
      "first-page": "2017",
      "DOI": "10.1099/0022-1317-70-8-2017",
      "volume": "70",
      "author": "Kimberlin R. H.",
      "year": "1989",
      "unstructured": "Kimberlin R. H., Walker C. A., Fraser H., J. Gen. Virol. 70, 2017 (1989).",
      "journal-title": "J. Gen. Virol."
    },
    {
      "key": "e_1_3_1_36_2",
      "doi-asserted-by": "crossref",
      "first-page": "1213",
      "DOI": "10.1101/gad.6.7.1213",
      "volume": "6",
      "author": "Hecker R.",
      "year": "1992",
      "unstructured": "Hecker R., et al., Genes Dev. 6, 1213 (1992).",
      "journal-title": "Genes Dev."
    },
    {
      "key": "e_1_3_1_37_2",
      "doi-asserted-by": "crossref",
      "first-page": "9936",
      "DOI": "10.1073/pnas.91.21.9936",
      "volume": "91",
      "author": "Telling G. C.",
      "year": "1994",
      "unstructured": "Telling G. C., et al., Proc. Natl. Acad. Sci. U.S.A. 91, 9936 (1994).",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
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      "key": "e_1_3_1_38_2",
      "doi-asserted-by": "crossref",
      "first-page": "743",
      "DOI": "10.1083/jcb.110.3.743",
      "volume": "110",
      "author": "Borchelt D. R.",
      "year": "1990",
      "unstructured": "Borchelt D. R., Scott M., Taraboulos A., Stahl N., Prusiner S. B., J. Cell Biol. 110, 743 (1990);",
      "journal-title": "J. Cell Biol."
    },
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      "key": "e_1_3_1_38_3",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)55257-1"
    },
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      "key": "e_1_3_1_39_2",
      "doi-asserted-by": "crossref",
      "first-page": "10940",
      "DOI": "10.1073/pnas.89.22.10940",
      "volume": "89",
      "author": "Gasset M.",
      "year": "1992",
      "unstructured": "Gasset M., et al., Proc. Natl. Acad. Sci. U.S.A. 89, 10940 (1992).",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
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      "key": "e_1_3_1_40_2",
      "first-page": "7139",
      "volume": "91",
      "author": "Huang Z.",
      "year": "1994",
      "unstructured": "Huang Z., et al., ibid. 91, 7139 (1994).",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_41_2",
      "doi-asserted-by": "crossref",
      "first-page": "63",
      "DOI": "10.1006/abio.1996.0132",
      "volume": "236",
      "author": "Pergami P.",
      "year": "1996",
      "unstructured": "Pergami P., Jaffe H., Safar J., Anal. Biochem. 236, 63 (1996).",
      "journal-title": "Anal. Biochem."
    },
    {
      "key": "e_1_3_1_42_2",
      "doi-asserted-by": "crossref",
      "first-page": "514",
      "DOI": "10.1006/jmbi.1995.0395",
      "volume": "250",
      "author": "Zhang H.",
      "year": "1995",
      "unstructured": "Zhang H., et al., J. Mol. Biol. 250, 514 (1995).",
      "journal-title": "J. Mol. Biol."
    },
    {
      "key": "e_1_3_1_43_2",
      "first-page": "362",
      "volume": "245",
      "author": "Sch\u00e4tzl H. M.",
      "year": "1995",
      "unstructured": "Sch\u00e4tzl H. M., Da Costa M., Taylor L., Cohen F. E., Prusiner S. B., ibid. 245, 362 (1995);",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_43_3",
      "doi-asserted-by": "crossref",
      "first-page": "495",
      "DOI": "10.1101/SQB.1996.061.01.050",
      "volume": "61",
      "author": "Bamborough P.",
      "year": "1996",
      "unstructured": "Bamborough P., et al., Cold Spring Harbor Symp. Quant. Biol. 61, 495 (1996).",
      "journal-title": "Cold Spring Harbor Symp. Quant. Biol."
    },
    {
      "key": "e_1_3_1_44_2",
      "doi-asserted-by": "crossref",
      "first-page": "979",
      "DOI": "10.1016/0092-8674(93)90275-U",
      "volume": "73",
      "author": "Scott M.",
      "year": "1993",
      "unstructured": "Scott M., et al., Cell 73, 979 (1993).",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_1_45_2",
      "doi-asserted-by": "crossref",
      "first-page": "675",
      "DOI": "10.1038/380675a0",
      "volume": "380",
      "author": "Krakauer D. C.",
      "year": "1996",
      "unstructured": "Krakauer D. C., Pagel M., Southwood T. R. E., Zanotto P. M., Nature 380, 675 (1996).",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_46_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi952965e"
    },
    {
      "key": "e_1_3_1_47_2",
      "first-page": "3543",
      "volume": "36",
      "author": "Zhang H.",
      "year": "1997",
      "unstructured": "Zhang H., et al., ibid. 36, 3543 (1997).",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_48_2",
      "unstructured": "T. L. James et al. Proc. Natl. Acad. Sci. U.S.A. 94 10086 (1997)."
    },
    {
      "key": "e_1_3_1_49_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/382180a0"
    },
    {
      "key": "e_1_3_1_50_2",
      "doi-asserted-by": "crossref",
      "unstructured": "M. Billeter et al. Proc. Natl. Acad. Sci. U.S.A. 94 7281 (1997).",
      "DOI": "10.1073/pnas.94.14.7281"
    },
    {
      "key": "e_1_3_1_51_2",
      "doi-asserted-by": "crossref",
      "first-page": "282",
      "DOI": "10.1016/S0014-5793(97)00920-4",
      "volume": "413",
      "author": "Riek R.",
      "year": "1997",
      "unstructured": "Riek R., Hornemann S., Wider G., Glockshuber R., W\u00fcthrich K., FEBS Lett. 413, 282 (1997).",
      "journal-title": "FEBS Lett."
    },
    {
      "key": "e_1_3_1_52_2",
      "unstructured": "D. G. Donne et al. Proc. Natl. Acad. Sci. U.S.A. in press. The consensus sequence of octarepeats in the NH 2 -terminal region is [P(Q/H)GGG(G/\u2212)- WGQ]."
    },
    {
      "key": "e_1_3_1_53_2",
      "doi-asserted-by": "crossref",
      "unstructured": "Z. Huang S. B. Prusiner F. E. Cohen Folding Design 1 13 (1996).",
      "DOI": "10.1016/S1359-0278(96)00007-7"
    },
    {
      "key": "e_1_3_1_54_2",
      "doi-asserted-by": "crossref",
      "first-page": "21",
      "DOI": "10.1111/j.1432-1033.1988.tb14246.x",
      "volume": "176",
      "author": "Turk E.",
      "year": "1988",
      "unstructured": "Turk E., Teplow D. B., Hood L. E., Prusiner S. B., Eur. J. Biochem. 176, 21 (1988).",
      "journal-title": "Eur. J. Biochem."
    },
    {
      "key": "e_1_3_1_55_2",
      "doi-asserted-by": "crossref",
      "first-page": "15457",
      "DOI": "10.1073/pnas.93.26.15457",
      "volume": "93",
      "author": "Muramoto T.",
      "year": "1996",
      "unstructured": "Muramoto T., Scott M., Cohen F., Prusiner S. B., Proc. Natl. Acad. Sci. U.S.A. 93, 15457 (1996).",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "e_1_3_1_56_2",
      "doi-asserted-by": "crossref",
      "first-page": "349",
      "DOI": "10.1016/0092-8674(83)90168-X",
      "volume": "35",
      "author": "Prusiner S. B.",
      "year": "1983",
      "unstructured": "Prusiner S. B., et al., Cell 35, 349 (1983).",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_1_57_2",
      "doi-asserted-by": "crossref",
      "first-page": "7672",
      "DOI": "10.1021/bi00245a003",
      "volume": "30",
      "author": "Caughey B. W.",
      "year": "1991",
      "unstructured": "Caughey B. W., et al., Biochemistry 30, 7672 (1991);",
      "journal-title": "Biochemistry"
    },
    {
      "key": "e_1_3_1_57_3",
      "doi-asserted-by": "crossref",
      "first-page": "1",
      "DOI": "10.1073/pnas.90.1.1",
      "volume": "90",
      "author": "Gasset M.",
      "year": "1993",
      "unstructured": "Gasset M., Baldwin M. A., Fletterick R. J., Prusiner S. B., Proc. Natl. Acad. Sci. U.S.A. 90, 1 (1993);",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "e_1_3_1_57_4",
      "doi-asserted-by": "crossref",
      "first-page": "20276",
      "DOI": "10.1016/S0021-9258(20)80725-X",
      "volume": "268",
      "author": "Safar J.",
      "year": "1993",
      "unstructured": "Safar J., Roller P. P., Gajdusek D. C., Gibbs C. J., J. Biol. Chem. 268, 20276 (1993).",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "e_1_3_1_58_2",
      "doi-asserted-by": "crossref",
      "first-page": "3182",
      "DOI": "10.1073/pnas.90.8.3182",
      "volume": "90",
      "author": "Rogers M.",
      "year": "1993",
      "unstructured": "Rogers M., Yehiely F., Scott M., Prusiner S. B., Proc. Natl. Acad. Sci. U.S.A. 90, 3182 (1993).",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "e_1_3_1_59_2",
      "doi-asserted-by": "crossref",
      "first-page": "1255",
      "DOI": "10.1002/j.1460-2075.1996.tb00467.x",
      "volume": "15",
      "author": "Fischer M.",
      "year": "1996",
      "unstructured": "Fischer M., et al., EMBO J. 15, 1255 (1996).",
      "journal-title": "EMBO J."
    },
    {
      "key": "e_1_3_1_60_2",
      "unstructured": "D. Peretz et al. J. Mol. Biol. in press."
    },
    {
      "key": "e_1_3_1_61_2",
      "doi-asserted-by": "crossref",
      "first-page": "293",
      "DOI": "10.1016/0021-9975(68)90005-4",
      "volume": "78",
      "author": "Dickinson A. G.",
      "year": "1968",
      "unstructured": "Dickinson A. G., Meikle V. M. H., Fraser H., J. Comp. Pathol. 78, 293 (1968).",
      "journal-title": "J. Comp. Pathol."
    },
    {
      "key": "e_1_3_1_62_2",
      "doi-asserted-by": "crossref",
      "first-page": "392",
      "DOI": "10.1016/0968-0004(82)90182-7",
      "volume": "7",
      "author": "Kimberlin R. H.",
      "year": "1982",
      "unstructured": "Kimberlin R. H., Trends Biochem. Sci. 7, 392 (1982);",
      "journal-title": "Trends Biochem. Sci."
    },
    {
      "key": "e_1_3_1_62_3",
      "unstructured": "; A. G. Dickinson and G. W. Outram in Novel Infectious Agents and the Central Nervous System vol. 135 of Ciba Foundation Symposium G. Bock and J. Marsh Eds. (Wiley Chichester UK 1988);"
    },
    {
      "key": "e_1_3_1_62_4",
      "first-page": "153",
      "volume": "1",
      "author": "Kimberlin R. H.",
      "year": "1990",
      "unstructured": "Kimberlin R. H., Semin. Virol. 1, 153 (1990);",
      "journal-title": "Semin. Virol."
    },
    {
      "key": "e_1_3_1_62_5",
      "doi-asserted-by": "crossref",
      "first-page": "595",
      "DOI": "10.1099/0022-1317-72-3-595",
      "volume": "72",
      "author": "Bruce M. E.",
      "year": "1991",
      "unstructured": "Bruce M. E., McConnell I., Fraser H., Dickinson A. G., J. Gen. Virol. 72, 595 (1991);",
      "journal-title": "J. Gen. Virol."
    },
    {
      "key": "e_1_3_1_62_6",
      "doi-asserted-by": "crossref",
      "first-page": "679",
      "DOI": "10.1038/352679a0",
      "volume": "352",
      "author": "Weissmann C.",
      "year": "1991",
      "unstructured": "Weissmann C., Nature 352, 679 (1991);",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_62_7",
      "doi-asserted-by": "crossref",
      "first-page": "219",
      "DOI": "10.1006/neur.1996.0030",
      "volume": "5",
      "author": "Ridley R. M.",
      "year": "1996",
      "unstructured": "Ridley R. M., Baker H. F., Neurodegeneration 5, 219 (1996).",
      "journal-title": "Neurodegeneration"
    },
    {
      "key": "e_1_3_1_63_2",
      "doi-asserted-by": "crossref",
      "first-page": "213",
      "DOI": "10.1017/S0016672300002895",
      "volume": "13",
      "author": "Dickinson A. G.",
      "year": "1969",
      "unstructured": "Dickinson A. G., Meikle V. M., Genet. Res. 13, 213 (1969);",
      "journal-title": "Genet. Res."
    },
    {
      "key": "e_1_3_1_63_3",
      "doi-asserted-by": "crossref",
      "first-page": "79",
      "DOI": "10.1099/0022-1317-68-1-79",
      "volume": "68",
      "author": "Bruce M. E.",
      "year": "1987",
      "unstructured": "Bruce M. E., Dickinson A. G., J. Gen. Virol. 68, 79 (1987).",
      "journal-title": "J. Gen. Virol."
    },
    {
      "key": "e_1_3_1_64_2",
      "doi-asserted-by": "crossref",
      "first-page": "405",
      "DOI": "10.1098/rstb.1994.0036",
      "volume": "343",
      "author": "Bruce M.",
      "year": "1994",
      "unstructured": "Bruce M., et al., Philos. Trans. R. Soc. London Ser. B 343, 405 (1994).",
      "journal-title": "Philos. Trans. R. Soc. London Ser. B"
    },
    {
      "key": "e_1_3_1_65_2",
      "doi-asserted-by": "crossref",
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      "DOI": "10.1016/0092-8674(87)90134-6",
      "volume": "51",
      "author": "Westaway D.",
      "year": "1987",
      "unstructured": "Westaway D., et al., Cell 51, 651 (1987);",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_1_65_3",
      "first-page": "5528",
      "volume": "8",
      "author": "Carlson G. A.",
      "year": "1988",
      "unstructured": "Carlson G. A., et al., Mol. Cell. Biol. 8, 5528 (1988);",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "e_1_3_1_65_4",
      "doi-asserted-by": "crossref",
      "first-page": "5690",
      "DOI": "10.1073/pnas.91.12.5690",
      "volume": "91",
      "author": "Carlson G. A.",
      "year": "1994",
      "unstructured": "Carlson G. A., et al., Proc. Natl. Acad. Sci. U.S.A. 91, 5690 (1994).",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "e_1_3_1_66_2",
      "doi-asserted-by": "crossref",
      "first-page": "301",
      "DOI": "10.1016/0021-9975(68)90006-6",
      "volume": "78",
      "author": "Fraser H.",
      "year": "1968",
      "unstructured": "Fraser H., Dickinson A. G., J. Comp. Pathol. 78, 301 (1968).",
      "journal-title": "J. Comp. Pathol."
    },
    {
      "key": "e_1_3_1_67_2",
      "doi-asserted-by": "crossref",
      "first-page": "283",
      "DOI": "10.1099/0022-1317-78-1-283",
      "volume": "78",
      "author": "Carp R. I.",
      "year": "1997",
      "unstructured": "Carp R. I., Meeker H., Sersen E., J. Gen. Virol. 78, 283 (1997).",
      "journal-title": "J. Gen. Virol."
    },
    {
      "key": "e_1_3_1_68_2",
      "first-page": "329",
      "volume": "73",
      "author": "Bessen R. A.",
      "year": "1992",
      "unstructured": "Bessen R. A., Marsh R. F., ibid. 73, 329 (1992);",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_68_3",
      "doi-asserted-by": "crossref",
      "unstructured": "; J. Virol. 68 7859 (1994);",
      "DOI": "10.1128/jvi.68.12.7859-7868.1994"
    },
    {
      "key": "e_1_3_1_68_4",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/375698a0"
    },
    {
      "key": "e_1_3_1_69_2",
      "unstructured": "M. Scott et al. J. Virol. in press."
    },
    {
      "key": "e_1_3_1_70_2",
      "doi-asserted-by": "crossref",
      "first-page": "2839",
      "DOI": "10.1073/pnas.91.7.2839",
      "volume": "91",
      "author": "Monari L.",
      "year": "1994",
      "unstructured": "Monari L., et al., Proc. Natl. Acad. Sci. U.S.A. 91, 2839 (1994).",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "e_1_3_1_71_2",
      "doi-asserted-by": "crossref",
      "first-page": "767",
      "DOI": "10.1002/ana.410390613",
      "volume": "39",
      "author": "Parchi P.",
      "year": "1996",
      "unstructured": "Parchi P., et al., Ann. Neurol. 39, 767 (1996).",
      "journal-title": "Ann. Neurol."
    },
    {
      "key": "e_1_3_1_72_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/382779a0"
    },
    {
      "key": "e_1_3_1_73_2",
      "first-page": "119",
      "volume": "381",
      "author": "Stekel D. J.",
      "year": "1996",
      "unstructured": "Stekel D. J., Nowak M. A., Southwood T. R. E., ibid. 381, 119 (1996).",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_74_2",
      "doi-asserted-by": "crossref",
      "first-page": "199",
      "DOI": "10.1136/vr.128.9.199",
      "volume": "128",
      "author": "Wilesmith J. W.",
      "year": "1991",
      "unstructured": "Wilesmith J. W., Ryan J. B. M., Atkinson M. J., Vet. Rec. 128, 199 (1991).",
      "journal-title": "Vet. Rec."
    },
    {
      "key": "e_1_3_1_75_2",
      "first-page": "239",
      "volume": "2",
      "author": "Wilesmith J. W.",
      "year": "1991",
      "unstructured": "Wilesmith J. W., Semin. Virol. 2, 239 (1991);",
      "journal-title": "Semin. Virol."
    },
    {
      "key": "e_1_3_1_75_3",
      "doi-asserted-by": "crossref",
      "unstructured": "; R. H. Kimberlin in Bovine Spongiform Encephalopathy: The BSE Dilemma C. J. Gibbs Jr. Ed. (Springer New York 1996) pp. 155\u2013175.",
      "DOI": "10.1007/978-1-4612-2406-8_13"
    },
    {
      "key": "e_1_3_1_76_2",
      "unstructured": "W. Goldmann N. Hunter J. Manson J. Hope Proceedings of the VIIIth International Congress of Virology Berlin 26 to 31 August 1990 p. 284;"
    },
    {
      "key": "e_1_3_1_76_3",
      "doi-asserted-by": "crossref",
      "first-page": "201",
      "DOI": "10.1099/0022-1317-72-1-201",
      "volume": "72",
      "author": "Goldmann W.",
      "year": "1991",
      "unstructured": "Goldmann W., Hunter N., Martin T., Dawson M., Hope J., J. Gen. Virol. 72, 201 (1991).",
      "journal-title": "J. Gen. Virol."
    },
    {
      "key": "e_1_3_1_77_2",
      "doi-asserted-by": "crossref",
      "first-page": "602",
      "DOI": "10.1093/infdis/167.3.602",
      "volume": "167",
      "author": "Prusiner S. B.",
      "year": "1993",
      "unstructured": "Prusiner S. B., et al., J. Infect. Dis. 167, 602 (1993).",
      "journal-title": "J. Infect. Dis."
    },
    {
      "key": "e_1_3_1_78_2",
      "doi-asserted-by": "crossref",
      "first-page": "400",
      "DOI": "10.1136/vr.135.17.400",
      "volume": "135",
      "author": "Hunter N.",
      "year": "1994",
      "unstructured": "Hunter N., Goldmann W., Smith G., Hope J., Vet. Rec. 135, 400 (1994).",
      "journal-title": "Vet. Rec."
    },
    {
      "key": "e_1_3_1_79_2",
      "first-page": "472",
      "volume": "123",
      "author": "Fraser H.",
      "year": "1988",
      "unstructured": "Fraser H., McConnell I., Wells G. A. H., Dawson M., ibid. 123, 472 (1988);",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_79_3",
      "unstructured": "; M. Dawson G. A. H. Wells B. N. J. Parker ibid. 126 112 (1990); ___ and A. C. Scott ibid. 127 338 (1990); M. Bruce A. Chree I. McConnell J. Foster H. Fraser in Proceedings of the IXth International Congress of Virology Glasgow Scotland 1993 p. 93."
    },
    {
      "key": "e_1_3_1_80_2",
      "doi-asserted-by": "crossref",
      "first-page": "241",
      "DOI": "10.1016/S0021-9975(05)80039-8",
      "volume": "113",
      "author": "Robinson M. M.",
      "year": "1995",
      "unstructured": "Robinson M. M., et al., J. Comp. Pathol. 113, 241 (1995).",
      "journal-title": "J. Comp. Pathol."
    },
    {
      "key": "e_1_3_1_81_2",
      "unstructured": "J. Wilesmith unpublished data."
    },
    {
      "key": "e_1_3_1_82_2",
      "doi-asserted-by": "crossref",
      "first-page": "924",
      "DOI": "10.1056/NEJM199609263351303",
      "volume": "335",
      "author": "Hsich G.",
      "year": "1996",
      "unstructured": "Hsich G., Kenney K., Gibbs C. J., Lee K. H., Harrington M. G., N. Engl. J. Med. 335, 924 (1996).",
      "journal-title": "N. Engl. J. Med."
    },
    {
      "key": "e_1_3_1_83_2",
      "doi-asserted-by": "crossref",
      "first-page": "390",
      "DOI": "10.1038/336390a0",
      "volume": "336",
      "author": "Hope J.",
      "year": "1988",
      "unstructured": "Hope J., et al., Nature 336, 390 (1988);",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_83_3",
      "doi-asserted-by": "crossref",
      "first-page": "110",
      "DOI": "10.1212/WNL.40.1.110",
      "volume": "40",
      "author": "Serban D.",
      "year": "1990",
      "unstructured": "Serban D., Taraboulos A., DeArmond S. J., Prusiner S. B., Neurology 40, 110 (1990);",
      "journal-title": "Neurology"
    },
    {
      "key": "e_1_3_1_83_4",
      "doi-asserted-by": "crossref",
      "first-page": "7620",
      "DOI": "10.1073/pnas.89.16.7620",
      "volume": "89",
      "author": "Taraboulos A.",
      "year": "1992",
      "unstructured": "Taraboulos A., et al., Proc. Natl. Acad. Sci. U.S.A. 89, 7620 (1992);",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "e_1_3_1_83_5",
      "doi-asserted-by": "crossref",
      "first-page": "205",
      "DOI": "10.1016/S0166-0934(97)02197-6",
      "volume": "64",
      "author": "Grathwohl K.-U. D.",
      "year": "1997",
      "unstructured": "Grathwohl K.-U. D., Horiuchi M., Ishiguro N., Shinagawa M., J. Virol. Methods 64, 205 (1997).",
      "journal-title": "J. Virol. Methods"
    },
    {
      "key": "e_1_3_1_84_2",
      "first-page": "522",
      "volume": "129",
      "author": "Taylor K. C.",
      "year": "1991",
      "unstructured": "Taylor K. C., Vet. Rec. 129, 522 (1991);",
      "journal-title": "Vet. Rec."
    },
    {
      "key": "e_1_3_1_84_3",
      "unstructured": ". ID median infective dose."
    },
    {
      "key": "e_1_3_1_85_2",
      "doi-asserted-by": "crossref",
      "first-page": "1891",
      "DOI": "10.1099/0022-1317-73-8-1891",
      "volume": "73",
      "author": "Fraser H.",
      "year": "1992",
      "unstructured": "Fraser H., Bruce M. E., Chree A., McConnell I., Wells G. A. H., J. Gen. Virol. 73, 1891 (1992).",
      "journal-title": "J. Gen. Virol."
    },
    {
      "key": "e_1_3_1_86_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.275.5298.402"
    },
    {
      "key": "e_1_3_1_87_2",
      "doi-asserted-by": "crossref",
      "first-page": "543",
      "DOI": "10.1016/S0034-5288(18)34840-9",
      "volume": "4",
      "author": "Hunter G. D.",
      "year": "1963",
      "unstructured": "Hunter G. D., Millson G. C., Chandler R. L., Res. Vet. Sci. 4, 543 (1963);",
      "journal-title": "Res. Vet. Sci."
    },
    {
      "key": "e_1_3_1_87_3",
      "doi-asserted-by": "crossref",
      "first-page": "15",
      "DOI": "10.1093/infdis/117.1.15",
      "volume": "117",
      "author": "Eklund C. M.",
      "year": "1967",
      "unstructured": "Eklund C. M., Kennedy R. C., Hadlow W. J., J. Infect. Dis. 117, 15 (1967);",
      "journal-title": "J. Infect. Dis."
    },
    {
      "key": "e_1_3_1_87_4",
      "doi-asserted-by": "publisher",
      "DOI": "10.1099/0022-1317-34-2-295"
    },
    {
      "key": "e_1_3_1_87_5",
      "doi-asserted-by": "crossref",
      "first-page": "353",
      "DOI": "10.1002/ana.410110406",
      "volume": "11",
      "author": "Prusiner S. B.",
      "year": "1982",
      "unstructured": "Prusiner S. B., et al., Ann. Neurol. 11, 353 (1982).",
      "journal-title": "Ann. Neurol."
    },
    {
      "key": "#cr-split#-e_1_3_1_88_2.1",
      "unstructured": "U.S. Centers for Disease Control and Prevention Morb. Mortal. Wkly. Rep. 45 665 (1996)"
    },
    {
      "key": "#cr-split#-e_1_3_1_88_2.2",
      "doi-asserted-by": "crossref",
      "unstructured": "J. W. Ironside Amyloid Int. J. Exp. Clin. Invest. 4 66 (1997).",
      "DOI": "10.3109/13506129708995272"
    },
    {
      "key": "e_1_3_1_89_2",
      "doi-asserted-by": "crossref",
      "first-page": "403",
      "DOI": "10.1136/vr.132.16.403",
      "volume": "132",
      "author": "Baker H. F.",
      "year": "1993",
      "unstructured": "Baker H. F., Ridley R. M., Wells G. A. H., Vet. Rec. 132, 403 (1993).",
      "journal-title": "Vet. Rec."
    },
    {
      "key": "e_1_3_1_90_2",
      "doi-asserted-by": "crossref",
      "first-page": "743",
      "DOI": "10.1038/381743a0",
      "volume": "381",
      "author": "Lasm\u00e9zas C. I.",
      "year": "1996",
      "unstructured": "Lasm\u00e9zas C. I., et al., Nature 381, 743 (1996);",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_90_3",
      "unstructured": "; R. Ridley and H. Baker unpublished data."
    },
    {
      "key": "e_1_3_1_91_2",
      "doi-asserted-by": "crossref",
      "first-page": "657",
      "DOI": "10.1093/infdis/146.5.657",
      "volume": "146",
      "author": "Hadlow W. J.",
      "year": "1982",
      "unstructured": "Hadlow W. J., Kennedy R. C., Race R. E., J. Infect. Dis. 146, 657 (1982).",
      "journal-title": "J. Infect. Dis."
    },
    {
      "key": "e_1_3_1_92_2",
      "doi-asserted-by": "crossref",
      "unstructured": "J. Collinge et al. Nature 378 779 (1995).",
      "DOI": "10.1038/378779a0"
    },
    {
      "key": "e_1_3_1_93_2",
      "doi-asserted-by": "crossref",
      "unstructured": "G. J. Raymond et al. ibid. 388 285 (1997).",
      "DOI": "10.1038/40876"
    },
    {
      "key": "e_1_3_1_94_2",
      "first-page": "685",
      "volume": "383",
      "author": "Collinge J.",
      "year": "1996",
      "unstructured": "Collinge J., Sidle K. C. L., Meads J., Ironside J., Hill A. F., ibid. 383, 685 (1996).",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_95_2",
      "unstructured": "P. Parchi et al. ibid. 386 232 (1997); R. A. Somerville et al. ibid. p. 564."
    },
    {
      "key": "e_1_3_1_96_2",
      "doi-asserted-by": "crossref",
      "first-page": "1",
      "DOI": "10.1016/0003-9861(89)90409-8",
      "volume": "274",
      "author": "Haraguchi T.",
      "year": "1989",
      "unstructured": "Haraguchi T., et al., Arch. Biochem. Biophys. 274, 1 (1989);",
      "journal-title": "Arch. Biochem. Biophys."
    },
    {
      "key": "e_1_3_1_96_3",
      "doi-asserted-by": "crossref",
      "first-page": "8380",
      "DOI": "10.1021/bi00447a017",
      "volume": "28",
      "author": "Endo T.",
      "year": "1989",
      "unstructured": "Endo T., Groth D., Prusiner S. B., Kobata A., Biochemistry 28, 8380 (1989).",
      "journal-title": "Biochemistry"
    },
    {
      "key": "e_1_3_1_97_2",
      "doi-asserted-by": "crossref",
      "first-page": "53",
      "DOI": "10.1093/brain/91.1.53",
      "volume": "91",
      "author": "Hornabrook R. W.",
      "year": "1968",
      "unstructured": "Hornabrook R. W., Brain 91, 53 (1968);",
      "journal-title": "Brain"
    },
    {
      "key": "e_1_3_1_97_3",
      "doi-asserted-by": "crossref",
      "first-page": "1",
      "DOI": "10.1002/ana.410120102",
      "volume": "12",
      "author": "Prusiner S. B.",
      "year": "1982",
      "unstructured": "Prusiner S. B., Gajdusek D. C., Alpers M. P., Ann. Neurol. 12, 1 (1982);",
      "journal-title": "Ann. Neurol."
    },
    {
      "key": "e_1_3_1_97_4",
      "unstructured": "; P. Brown in Developments in Biological Standardization F. Brown Ed. (Karger Basel Switzerland 1993) vol. 80 pp. 91\u2013101."
    },
    {
      "key": "e_1_3_1_98_2",
      "doi-asserted-by": "crossref",
      "unstructured": "R. M. Glasse Trans. N.Y. Acad. Sci. Ser. 2 29 748 (1967);",
      "DOI": "10.1111/j.2164-0947.1967.tb02298.x"
    },
    {
      "key": "e_1_3_1_98_3",
      "doi-asserted-by": "crossref",
      "first-page": "449",
      "DOI": "10.1016/S0140-6736(68)90482-0",
      "author": "Mathews J. D.",
      "year": "1968",
      "unstructured": "Mathews J. D., Glasse R., Lindenbaum S., Lancet ii, 449 (1968).",
      "journal-title": "Lancet"
    },
    {
      "key": "e_1_3_1_99_2",
      "doi-asserted-by": "crossref",
      "first-page": "1683",
      "DOI": "10.1212/WNL.44.9.1683",
      "volume": "44",
      "author": "Chapman J.",
      "year": "1994",
      "unstructured": "Chapman J., Ben-Israel J., Goldhammer Y., Korczyn A. D., Neurology 44, 1683 (1994);",
      "journal-title": "Neurology"
    },
    {
      "key": "e_1_3_1_99_3",
      "doi-asserted-by": "crossref",
      "first-page": "607",
      "DOI": "10.1007/BF03401601",
      "volume": "1",
      "author": "Spudich S.",
      "year": "1995",
      "unstructured": "Spudich S., et al., Mol. Med. 1, 607 (1995).",
      "journal-title": "Mol. Med."
    },
    {
      "key": "e_1_3_1_100_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7909169"
    },
    {
      "key": "e_1_3_1_101_2",
      "doi-asserted-by": "crossref",
      "first-page": "619",
      "DOI": "10.1083/jcb.129.3.619",
      "volume": "129",
      "author": "Gorodinsky A.",
      "year": "1995",
      "unstructured": "Gorodinsky A., Harris D. A., J. Cell Biol. 129, 619 (1995);",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "e_1_3_1_101_3",
      "unstructured": "; A. Taraboulos et al. ibid. p. 121; M. Vey et al. Proc. Natl. Acad. Sci. U.S.A. 93 14945 (1996); K. Kaneko et al. ibid. 94 2333 (1997);"
    },
    {
      "key": "e_1_3_1_101_4",
      "doi-asserted-by": "crossref",
      "first-page": "6324",
      "DOI": "10.1074/jbc.272.10.6324",
      "volume": "272",
      "author": "Naslavsky N.",
      "year": "1997",
      "unstructured": "Naslavsky N., Stein R., Yanai A., Friedlander G., Taraboulos A., J. Biol. Chem. 272, 6324 (1997).",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "e_1_3_1_102_2",
      "doi-asserted-by": "crossref",
      "first-page": "1025",
      "DOI": "10.1099/0022-1317-74-6-1025",
      "volume": "74",
      "author": "Hunter N.",
      "year": "1993",
      "unstructured": "Hunter N., Goldmann W., Benson G., Foster J. D., Hope J., J. Gen. Virol. 74, 1025 (1993);",
      "journal-title": "J. Gen. Virol."
    },
    {
      "key": "e_1_3_1_102_3",
      "first-page": "989",
      "volume": "75",
      "author": "Goldmann W.",
      "year": "1994",
      "unstructured": "Goldmann W., Hunter N., Smith G., Foster J., Hope J., ibid. 75, 989 (1994);",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_102_4",
      "doi-asserted-by": "crossref",
      "first-page": "959",
      "DOI": "10.1101/gad.8.8.959",
      "volume": "8",
      "author": "Westaway D.",
      "year": "1994",
      "unstructured": "Westaway D., et al., Genes Dev. 8, 959 (1994);",
      "journal-title": "Genes Dev."
    },
    {
      "key": "e_1_3_1_102_5",
      "doi-asserted-by": "crossref",
      "first-page": "509",
      "DOI": "10.1099/0022-1317-76-3-509",
      "volume": "76",
      "author": "Belt P. B. G. M.",
      "year": "1995",
      "unstructured": "Belt P. B. G. M., et al., J. Gen. Virol. 76, 509 (1995);",
      "journal-title": "J. Gen. Virol."
    },
    {
      "key": "e_1_3_1_102_6",
      "unstructured": "; C. Clousard et al. ibid. p. 2097; T. Ikeda et al. ibid. p. 2577;"
    },
    {
      "key": "e_1_3_1_102_7",
      "doi-asserted-by": "crossref",
      "first-page": "59",
      "DOI": "10.1136/vr.140.3.59",
      "volume": "140",
      "author": "Hunter N.",
      "year": "1997",
      "unstructured": "Hunter N., Moore L., Hosie B. D., Dingwall W. S., Greig A., Vet. Rec. 140, 59 (1997);",
      "journal-title": "Vet. Rec."
    },
    {
      "key": "e_1_3_1_102_8",
      "doi-asserted-by": "crossref",
      "first-page": "137",
      "DOI": "10.1038/386137a0",
      "volume": "386",
      "author": "Hunter N.",
      "year": "1997",
      "unstructured": "Hunter N., et al., Nature 386, 137 (1997);",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_102_9",
      "unstructured": "; K. I. O'Rourke et al. J. Gen. Virol. 78 975 (1997)."
    },
    {
      "key": "e_1_3_1_103_2",
      "doi-asserted-by": "crossref",
      "first-page": "75",
      "DOI": "10.1038/hdy.1962.4",
      "volume": "17",
      "author": "Parry H. B.",
      "year": "1962",
      "unstructured": "Parry H. B., Heredity 17, 75 (1962);",
      "journal-title": "Heredity"
    },
    {
      "key": "e_1_3_1_103_3",
      "unstructured": "; in Scrapie Disease in Sheep D. R. Oppenheimer Ed. (Academic Press New York 1983) pp. 31\u201359."
    },
    {
      "key": "e_1_3_1_104_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(93)90360-3"
    },
    {
      "key": "e_1_3_1_105_2",
      "doi-asserted-by": "crossref",
      "first-page": "10608",
      "DOI": "10.1073/pnas.90.22.10608",
      "volume": "90",
      "author": "Prusiner S. B.",
      "year": "1993",
      "unstructured": "Prusiner S. B., et al., Proc. Natl. Acad. Sci. U.S.A. 90, 10608 (1993).",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "e_1_3_1_106_2",
      "doi-asserted-by": "crossref",
      "first-page": "295",
      "DOI": "10.1038/370295a0",
      "volume": "370",
      "author": "Collinge J.",
      "year": "1994",
      "unstructured": "Collinge J., et al., Nature 370, 295 (1994);",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_106_3",
      "doi-asserted-by": "crossref",
      "first-page": "2403",
      "DOI": "10.1073/pnas.93.6.2403",
      "volume": "93",
      "author": "Lledo P.-M.",
      "year": "1996",
      "unstructured": "Lledo P.-M., Tremblay P., DeArmond S. J., Prusiner S. B., Nicoll R. A., Proc. Natl. Acad. Sci. U.S.A. 93, 2403 (1996);",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "e_1_3_1_106_4",
      "doi-asserted-by": "crossref",
      "first-page": "528",
      "DOI": "10.1038/380528a0",
      "volume": "380",
      "author": "Sakaguchi S.",
      "year": "1996",
      "unstructured": "Sakaguchi S., et al., Nature 380, 528 (1996);",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_106_5",
      "unstructured": "; I. Tobler et al. ibid. p. 639."
    },
    {
      "key": "e_1_3_1_107_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7909170"
    },
    {
      "key": "e_1_3_1_107_3",
      "first-page": "880",
      "volume": "268",
      "author": "Chernoff Y. O.",
      "year": "1995",
      "unstructured": "Chernoff Y. O., Lindquist S. L., Ono B.-i., Inge-Vechtomov S. G., Liebman S. W., ibid. 268, 880 (1995) ;",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_107_4",
      "doi-asserted-by": "crossref",
      "first-page": "1375",
      "DOI": "10.1093/genetics/144.4.1375",
      "volume": "144",
      "author": "Derkatch I. L.",
      "year": "1996",
      "unstructured": "Derkatch I. L., Chernoff Y. O., Kushnirov V. V., Inge-Vechtomov S. G., Liebman S. W., Genetics 144, 1375 (1996);",
      "journal-title": "Genetics"
    },
    {
      "key": "e_1_3_1_107_5",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)80264-0"
    },
    {
      "key": "e_1_3_1_107_6",
      "doi-asserted-by": "crossref",
      "first-page": "9773",
      "DOI": "10.1073/pnas.94.18.9773",
      "volume": "94",
      "author": "Coustou V.",
      "year": "1997",
      "unstructured": "Coustou V., Deleu C., Saupe S., Begueret J., Proc. Natl. Acad. Sci. U.S.A. 94, 9773 (1997).",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "e_1_3_1_108_2",
      "doi-asserted-by": "crossref",
      "unstructured": "C.-Y. King et al. Proc. Natl. Acad. Sci. U.S.A. 94 6618 (1997).",
      "DOI": "10.1073/pnas.94.13.6618"
    },
    {
      "key": "e_1_3_1_109_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.277.5324.381"
    },
    {
      "key": "e_1_3_1_110_2",
      "doi-asserted-by": "crossref",
      "first-page": "673",
      "DOI": "10.1016/0092-8674(90)90134-Z",
      "volume": "63",
      "author": "Prusiner S. B.",
      "year": "1990",
      "unstructured": "Prusiner S. B., et al., Cell 63, 673 (1990);",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_1_110_3",
      "unstructured": "; D. Groth and S. B. Prusiner unpublished data."
    },
    {
      "key": "e_1_3_1_111_2",
      "unstructured": "G. Telling et al. in preparation."
    },
    {
      "key": "e_1_3_1_112_2",
      "unstructured": "I thank F. E. Cohen and S. J. DeArmond for many stimulating discussions and their help in preparing this manuscript. Human specimens were kindly provided by J. Ironside R. Will and J. Bell. Supported by grants from NIH (NS14069 AG08967 P41-RR01081 AG02132 and NS22786) the International Human Frontiers of Science Program and the American Health Assistance Foundation as well as by gifts from the Sherman Fairchild Foundation the G. Harold and Leila Y. Mathers Foundation the Bernard Osher Foundation and Centeon Inc."
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