1887

Abstract

The molecular basis of differences among scrapie strains is unknown. The prion theory posits that there are differences in the conformation of the host protease-resistant protein (PrP) molecules and that these differences are responsible for scrapie strains. A corollary of this theory is that the origin of host PrP variation resides in different neuronal cell types. To assess this concept, preparations from three brain regions (cerebrum, cerebellum and olfactory bulb) and from spleen were passaged in C57BL mice by intracerebral injection. After three passages of three scrapie strains in this manner, homogenates of each brain region and spleen were tested for several of the characteristics that distinguish the three strains: (1) the rank order of incubation periods in C57BL mice, (2) induction of obesity in SJL mice and (3) comparative incubation periods in mice with three genotypes for the scrapie incubation period marker. Analysis revealed that virtually all of the criteria that distinguished the three strains prior to passages of the three brain regions and spleen were retained after this series of passages. This finding argues against cellular-based PrP differences providing a basis for strain specificity.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-78-1-283
1997-01-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/78/1/9010315.html?itemId=/content/journal/jgv/10.1099/0022-1317-78-1-283&mimeType=html&fmt=ahah

References

  1. Bessen R. A., Marsh R. F. 1992; Biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent. Journal of Virology 66:2096–2101
    [Google Scholar]
  2. Bolton D. C., McKinley M. P., Prusiner S. B. 1982; Identification of a protein that purifies with the scrapie prion. Science 218:1309–1311
    [Google Scholar]
  3. Bruce M. E., McBride P. A., Farquhar C. F. 1989; Precise targeting of the pathology of the sialoglycoprotein, PrP, and vacuolar degeneration in mouse scrapie. Neuroscience Letters 102:1–6
    [Google Scholar]
  4. Bryk A. S., Raudenbush S. W. 1992 Hierarchical Linear Models: Applications and Data Analysis Methods Newbury Park: Sage Publications;
    [Google Scholar]
  5. Carlson G. A., Eberling C., Yang S.-L., Telling G., Torchia M., Groth D., Westaway D., DeArmond S., Prusiner S. B. 1994; Prion isolate specified allotypic interactions between the cellular and scrapie prion proteins in congenic and transgenic mice. Proceedings of the National Academy of Sciences, USA 91:5690–5694
    [Google Scholar]
  6. Carp R. I., Callahan S. M. 1986; Scrapie incubation periods and endpoint titers in mouse strains differing at the H-2D locus. Intervirology 26:85–92
    [Google Scholar]
  7. Carp R. I., Rubenstein R. 1991; Diversity and significance of scrapie strains. Seminars in Virology 2:203–213
    [Google Scholar]
  8. Carp R. I., Callahan S. M., Sersen E. A., Moretz R. C. 1984; Preclinical changes in weight of scrapie-infected mice as a function of scrapie agent-mouse strain combination. Intervirology 21:61–69
    [Google Scholar]
  9. Carp R. I., Moretz R. C., Natelli M., Dickinson A. G. 1987; Genetic control of scrapie: incubation period and plaque formation in I mice. Journal of General Virology 68:401–407
    [Google Scholar]
  10. Carp R. I., Kascsak R. J., Ye X., Kozlowski P. B., Kozielski R., Diedrich J. F., Haase A. T. 1993; Possible roles for astroglia and microglia in the pathogenesis of unconventional slow infections. In Biology and Pathology of Astrocyte-Neuron Interactions pp. 417–429 Fedoroff S., Juurlink B. H. J., Doucette R. Edited by New York: Plenum;
    [Google Scholar]
  11. Carp R. I., Kascsak R. J., Rubenstein R., Merz P. A. 1994a; The puzzle of PrPSc and infectivity - do the pieces fit?. Trends in Neurosciences 17:148–149
    [Google Scholar]
  12. Carp R. I., Ye X., Kascsak R. J., Rubenstein R. 1994b; The nature of the scrapie agent. Biological characteristics of scrapie in different scrapie strain-host combinations. In Slow Infections of the Central Nervous System, the Legacy of Dr. Bjorn Sigurdsson, Annals of the New York Academy of Sciences 724 pp. 221–234 Björnsson J., Carp R. I., Love A., Wisniewski H. M. Edited by New York: The New York Academy of Sciences;
    [Google Scholar]
  13. Casaccia-Bonnefil P., Kascsak R. J., Fersko R., Callahan S. M., Carp R. I. 1993; Brain regional distribution of prion protein PrP27-30 in mice stereotaxically microinjected with different strains of scrapie. Journal of Infectious Diseases 167:7–12
    [Google Scholar]
  14. Cohen F. E., Pan K.-M., Hwang Z., Baldwin M., Fletterick R. J., Prusiner S. B. 1994; Structural clues to prion replication. Science 264:530–531
    [Google Scholar]
  15. David S., Ness R. 1993; Heterogeneity of reactive astrocytes. In Biology and Pathology of Astrocyte-Neuron Interactions pp. 303–313 Federoff S., Juurlink B. H. J., Doucette R. Edited by New York: Plenum;
    [Google Scholar]
  16. DeArmond S. J., Mobley W. C., Demott D. L., Barry R. A., Beckstead J. H., Prusiner S. B. 1987; Chang es in the localization of brain prion proteins during scrapie infection. Neurology 37:1271–1280
    [Google Scholar]
  17. DeArmond S. J., Yang S.-L., Lee A., Bowler R., Taraboulos A., Groth D., Prusiner S. B. 1993; Three scrapie prion isolates exhibit different accumulation patterns of the prion protein scrapie isoform. Proceedings of the National Academy of Sciences, USA 90:6449–6453
    [Google Scholar]
  18. Dickinson A. G., Fraser H. 1979; An assessment of the genetics of scrapie in sheep and mice. In Slow Transmissible Diseases of the Nervous System 1 pp. 367–385 Prusiner S. B., Hadlow W. J. Edited by New York: Academic Press;
    [Google Scholar]
  19. Dickinson A. G., Meikle V. M. H. 1971; Host-genotype and agent effects on scrapie incubation: change in allelic interaction with different strains of agent. Molecular & General Genetics 112:73–79
    [Google Scholar]
  20. Dickinson A. G., Outram G. W. 1983; Operational limitations in the characteristics of the infective units of scrapie. In Virus Non-Conventionnels et Affections du Systeme Nerveux Central pp. 3–16 Court L. A., Cathala F. Edited by Paris: Masson;
    [Google Scholar]
  21. Diedrich J. F., Bendheim P. E., Kim Y. S., Carp R. I., Haase A. T. 1991; Scrapie-associated prion protein accumulates in astrocytes during scrapie infection. Proceedings of the National Academy of Sciences, USA 88:375–379
    [Google Scholar]
  22. Hecker R., Taraboulos A., Scott M., Pan K.-M., Yang S.-L., Torchia M., Jendroska K., DeArmond S. J., Prusiner S. B. 1992; Replication of distinct scrapie prion isolates is region specific in brains of transgenic mice and hamsters. Genes & Development 6:1213–1228
    [Google Scholar]
  23. Jendroska K., Heinzel F. P., Torchia M., Stowring L., Kretzschmar H. A., Kon A., Stern B. S., Prusiner S. B., DeArmond S. J. 1991; Proteinase-resistant prion protein accumulation in Syrian hamster brain correlates with regional pathology and scrapie infectivity. Neurology 41:1482–1490
    [Google Scholar]
  24. Kascsak R. J., Rubenstein R., Carp R. I. 1991; Evidence for biological and structural diversity among scrapie strains. Current Topics in Microbiology and Immunology 172:139–150
    [Google Scholar]
  25. Kim Y. S., Carp R. I., Callahan S. M., Wisniewski H. M. 1987; Scrapie-induced obesity in mice. Journal of Infectious Diseases 156:402–405
    [Google Scholar]
  26. Kim Y. S., Carp R. I., Callahan S. M., Wisniewski H. M. 1988; Adrenal involvement in scrapie-induced obesity. Proceedings of the Society for Experimental Biology and Medicine 189:21–27
    [Google Scholar]
  27. Kimberlin R. H., Walker C. A. 1983; Invasion of the CNS by scrapie agent and its spread to different parts of the brain. In Virus Non Conventionnels et Affections du Systeme Nerveux Central pp. 17–33 Court L. A., Cathala F. Edited by Paris: Masson;
    [Google Scholar]
  28. Kretzschmar H. A., Prusiner S. B., Stowring L. E., DeArmond S. J. 1986; Scrapie prion proteins are synthesized in neurons. American Journal of Pathology 122:1–5
    [Google Scholar]
  29. Lawson L. J., Perry V. H., Dri P., Gordon S. 1990; Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 39:151–170
    [Google Scholar]
  30. Priola S. A., Chesebro B. 1995; A single hamster PrP amino acid blocks conversion to protease-resistant PrP in scrapie-infected mouse neuroblastoma cells. Journal of Virology 69:7754–7758
    [Google Scholar]
  31. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144
    [Google Scholar]
  32. Prusiner S. B. 1991; Molecular biology of prion disease. Science 252:1515–1522
    [Google Scholar]
  33. Prusiner S. B., Scott M., Foster D., Pan K.-M., Groth D. F., Mirenda C. A., Torchia M., Yang S.-L., Serban D., Carlson G. A., Hoppe P. C., Westaway D., DeArmond S. J. 1990; Transgenic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63:673–686
    [Google Scholar]
  34. Rubenstein R., Merz P. A., Kascsak R. J., Scalici C. L., Papini M. C., Carp R. I., Kimberlin R. H. 1991; Scrapie-infected spleens : analysis of infectivity, scrapie-associated fibrils, and protease-resistant proteins. Journal of Infectious Diseases 164:29–35
    [Google Scholar]
  35. Taraboulos A., Jendroska K., Serban D., Yang S.-L., DeArmond S. J., Prusiner S. B. 1992; Regional mapping of prion proteins in brain. Proceedings ofthe National Academy ofSciences, USA 89:7620–7624
    [Google Scholar]
  36. Weissman C. 1991a; The prion’s progress. Nature 349:569–571
    [Google Scholar]
  37. Weissman C. 1991b; A ‘unified theory’ of prion propagation. Nature 352:379–383
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-78-1-283
Loading
/content/journal/jgv/10.1099/0022-1317-78-1-283
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error