Abstract
More than 30 years ago PATTISON and MILLSON (1961) reported the occurrence of two distinct constellations of clinical signs, labeled nervous or drowsy, in goats experimentally infected with scrapie. These syndromes were reproducible through subsequent intracerebral inoculations, suggesting the existence of “true breeding” variants of scrapie agent. Subsequent transmissions of both goat and sheep scrapie into experimental rodents set the stage for isolation of multiple scrapie “strains” (ZLOTNIT 1965). The existence of scrapie isolates that exhibit distinct and stable properties in the same inbred mouse strain provided evidence for agent-specified information, thought to be encoded by a polynucleotide (BRUCE and DICKINSON 1987). The existence of microbiological strains of agent continues to be presented as an argument against the concept of a proteinaceous infectious particle devoid of functional nucleic acid. The only known functional component of prions is PrPSc, a disease-specific, posttranslational derivative of the normal prion protein isoform, PrPc (PRUSINER 1991). β-pleated sheet is a major secondary structure of PrPSc, in contrast to the predominance of α-helix in PrPc, and the two isoforms may differ only in their conformations (Pan et al. 1993; Safar et al. 1993). PrPSc is certainly necessary, and possibly sufficient, for transmission of scrapie. No scrapie-specific nucleic acid has ever been detected in purified prion preparations, and to be present at one molecule per infectious unit a prion-specific nucleic acid would need to have fewer than 50 nucleotides (Kellings et al. 1992). Properties of viral, bacteria and fungal strains are most often attributed directly to mutations within their nucleic acid genomes, with the interesting exception of prion-like epigenetic phenomena in yeast (WICKNER 1994). If prions are devoid of functional nucleic acid, other mechanisms must account for the existence of strains. The first part of this report emphasizes the role of PrP in determining strain properties, followed by discussion of other components that may be involved.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Bessen RA, Marsh RF (1992) Biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent. J Virol 66:2096–2101
Bolton DC, McKinley MP, Prusiner SB (1982) Identification of a protein that purifies with the scrapie prion. Science 218:1309–1311
Bruce ME, Dickinson AG (1985) Genetic control of amyloid plaque production and incubation period in scrapie-infected mice. J Neuropathol Exp Neurol 44:285–194
Bruce ME, Dickinson AG (1987) Biological evidence that the scrapie agent has an independent genome. J Gen Virol 68:79–89
Bruce ME, Dickinson AG, Fraser H (1976) Cerebral amyloidosis in scrapie in the mouse: effect of agent strain and mouse genotype. Neuropathol Appl Neurobiol 2: 471 – 478
Bruce ME, McConnell I, Fraser H, Dickinson, AG (1991) Disease characteristics of different strains of scrapie in Sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis. J Gen Virol 72: 595 – 603
Carlson GA, Kingsbury DT, Goodman PA, Coleman S, Marshall ST, DeArmond S, Westaway D, Prusiner SB (1986) Linkage of prion protein and scrapie incubation time genes. Cell 46: 503 – 511
Carlson GA, Goodman PA, Lovett M, Taylor BA, Marshall ST, Peterson-Torchia M, Westaway D, Prusiner SB (1988) Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time. Mol Cell Biol 8: 5528 – 5540
Carlson GA, Westway D, DeArmond SJ, Peterson-Torchia M, Prusiner SB(1989) Primary structure of prion protein may modify scrapie isolate properties. Proc Natl Acad Sci USA 86: 7475 – 7479
Carlson GA, Ebeling C, Torchia M, Westaway D, Prusiner SB (1993) Delimiting the location of the scrapie prion incubation time gene on chromosome 2 of the mouse. Genetics 133: 379 – 988
Carlson GA, DeArmond SJ, Torchia M, Westaway D, Prusiner SB (1994a) Genetics of prion diseases and prion diversity in mice. Philos Trans R Soc Lond [B] 343: 363 – 369
Carlson GA, Ebeling C, Yang SL, Telling G, Torchia M, Groth D, Westaway D, DeArmond SJ, Prusiner SB (1994b) Prion isolate specified allotypic interactions between the cellular and scrapie prion proteins in congenic and transgenic mice. Proc Natl Acad Sci USA 91: 5690 – 5694
DeArmond SJ, Yang S-L, Lee A, Bowler R, Taraboulos A, Groth D, Prusiner SB (1993) Three scrapie prion isolates exhibit different accumulation patterns of the prion protein scrapie isoform. Proc Natl Acad Sci USA 90: 6449 – 6453
Dickinson AG, Fraser H (1977) Scrapie: pathogenesis in inbred mice: an assessment of host control and response involving many strains of agent. In: Katz M, Meuler V (eds) Slow virus infections of CNS. Springer, Berlin Heidelberg New York, pp 3 – 14
Dickinson AG, MacKay JMK (1964) Genetical control of the incubation period in mice of the neurological disease, scrapie. Heredity 19: 279 – 288
Dickinson AG, Meikle VMH (1971) Host-genotype and agent effects in scrapie incubation: change in allelic interaction with different strains of agent. Mol Gen Genet 112: 73 – 79
Dickinson AG, Outram GW (1979) The scrapie replication-site hypothesis and its implications for pathogenesis. In: Prusiner SB, Hadlow WJ (eds) Slow transmissible diseases of the nervous system, vol 2. Academic, New York, pp 13 – 31
Dickinson AG, Meikle VMH, Fraser HG (1968) Identification of a gene which controls the incubation period of some strains of scrapie agent in mice. J Comp Pathol 78: 293 – 299
Goldfarb LG, Petersen RB, Tabaton M, Brown P, LeBlanc AC, Montagna P, Cortelli P, Julien J, Vital C, Pendelbury WW, Haltia M, Wills PR, Hauw JJ, McKeever PE, Monare L, Schrank B, Swergold GD, Autilio-Gambetti L, Gajdusek DC, Lugaresi E, Gambetti P (1992) Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by DNA polymorphism. Science 258: 806 – 808
Goldman W, Hunter N, Foster JD, Salbaum JM, Beyreuther K, Hope J (1990) Two alleles of a neural protein gene linked to scrapie in sheep. Proc Natl Acad Sci USA 87: 2476 – 2480
Kascsak RJ, Rubenstein R, Merz PA, Carp RI, Robakis NK, Wisniewski HM, Diringer H (1986) Immunological comparison of scrapie-associated fibrils isolated from animals infected with four different scrapie strains J Virol 59: 676 – 683
Kellings K, Meyer N, Mirenda C, Prusiner SB, Riesner D (1992) Further analysis of nucleic acids in purified scrapie prion preparations by improved return refocussing gel electrophoresis (RRGE). J Gen Virol 73: 1025 – 1029
Marsh RF, Sipe JC, Morse SS, Hanson RP (1976) Transmissible mink encephalopathy reduced spongiform degeneration in aged mink of the Chediak-Higashi genotype. Lab Invest 34: 381 – 386
Monari L, Chen SG, Brown P, Parchi P, Petersen RB, Mikol J, Gray F, Cortelli P, Montagna P, Ghetti B, Goldfarb LG, Gajdusek DC, Lugaresi E, Gambetti P, Autilio-Gambetti L (1994) Fatal familial insomnia and familial Creutzfeldt-Jakob disease: different prion proteins determined by a DNA polymorphism. Proc Natl Acad Sci USA 91: 2839 – 2842
Oesch B, Westaway D, Wachli M, McKinley MP, Kent SBH, Aebersold R, Barry RA, Tempst P, Teplow DB, Hood L, Prusiner SB, Weissmann C (1985) A cellular gene encodes scrapie PrP 27–30 protein. Cell 40: 735 – 746
Palmer MS, Dryden AJ, Hughes JT, Collinge J (1991) Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease. Nature 352: 340 – 342
Pan K-M, Baldwin M, Nguyen J, Gasset M, Serban A, Groth D, Melhorn I, Huang Z, Fletterick RJ, Cohen FE, Prusiner SB (1993) Conversion of α-helices into β-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci USA 90: 10962 – 10966
Pattison IH, Millson GC (1961) Scrapie produced experimentally in goats with special reference to the clinical syndrome. J Comp Pathol 71: 101 – 108
Prusiner SB (1991) Molecular biology of prion diseases. Science 252: 1515 – 1522
Prusiner SB, Scott M, Foster D, Pan K-M, Groth D, Mirenda C, Torchia M, Yang S-L, Serban D, Carlson GA, Hoppe PC, Westaway D, DeArmond SJ (1990) Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63: 673 – 686
Safar J, Roller PP, Gajdusek DC, Gibbs CJ Jr. (1993) Conformation transitions, dissociation, and unfolding of scrapie amyloid (prion) protein. J Biol Chem 269: 20276 – 20284
Scott M, Foster D, Mirenda C, Serban D, Coufal F, Wachli M, lorchia M, Groth D, Carlson G, DeArmond SJ, Westaway D, Prusiner SB (1989) Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques. Cell 59: 847 – 857
Scott M, Groth D, Foster D, Torchia M, Yang S-L, DeArmond SJ, Prusiner SB (1993) Propagation of prions with artificial properties in transgenic mice expressing chimeric PrP genes. Cell 73: 979 – 988
Sparkes RS, Simon M, Cohn VH, Fournier REK, Lem J, Klisak I, Heinzmann C, Blatt C, Lucero M, Mohandas T, DeArmond SJ, Westaway D, Prusiner SB, Weiner LP (1986) Assignment of the human and mouse prion protein genes to homologous chromosomes. Proc Natl Acad Sci USA 83: 7358 – 7362
Taraboulos A, Jendroska K, Serban D, Yang S-L, DeArmond SJ, Prusiner SB (1992) Regional mapping of prion proteins in brains. Proc Natl Acad Sci USA 89: 7620 – 7624
Westaway D, Goodman PA, Mirenda CA, McKinley MP, Carlson GA, Prusiner SB (1987) Distinct prion proteins in short and long scrapie incubation period mice. Cell 51: 651 – 662
Westaway D, Mirenda CA, Foster D, Zebarjadian Y, Scott M, Torchia M, Yang SL, Serban H, DeArmond SJ, Ebeling C, Prusiner SB, Carlson GA (1991) Paradoxical shortening of scrapie incubation times by expression of prion protein transgenes derived from long incubation time mice. Neuron 7: 59 – 68
Westaway D, Cooper C, Turner S, Da Costa M, Carlson GA, Prusiner SB (1994a) Structure and polymorphism of the mouse prion protein gene. Proc Natl Acad Sci USA 91: 6418 – 6422
Westaway D, Zuliani V, Cooper CM, Da Costa M, Neuman S, Jenny AL, Detwiler L, Prusiner SB (1994b) Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie. Genes 8: 959 – 969
Wickner RB (1994) [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. Science 264: 566 – 569
Zlotnik I (1965) Observations on the experimental transmission of scrapie of various origins to laboratory animals. In: Slow, latent, and temperate virus infections. NINDB Monogr 2: 237 – 248
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Carlson, G.A. (1996). Prion Strains. In: Prusiner, S.B. (eds) Prions Prions Prions. Current Topics in Microbiology and Immunology, vol 207. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60983-1_4
Download citation
DOI: https://doi.org/10.1007/978-3-642-60983-1_4
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-64640-9
Online ISBN: 978-3-642-60983-1
eBook Packages: Springer Book Archive