1887

Abstract

Scrapie strain replication in the nerve growth factor-induced, differentiated PC12 cell culture system was examined. Differences in replication between mouse-derived agents were demonstrated, with the 139A scrapie strain yielding 100- to 1000-fold higher levels of infectivity than the ME7 scrapie strain. Replication was not detected in PC12 cells infected with either the hamster-derived 263K or rat-derived 139R scrapie strains. Studies on the neurotransmitters in infected PC12 cells demonstrated that the adrenergic pathway was unchanged but the cholinergic pathway was altered. Furthermore, the degree of alteration correlated with the level of scrapie strain replication. Comparison of infectivity titres and enzymatic changes in ME7-infected PC12 cells with those in Chandler agent-infected mouse neuroblastoma cells suggests that the significant changes in neurotransmitter levels in cultures exhibiting low titres of infectivity involve factors in addition to strain replication. The variation in the range of scrapie strain replication in PC12 cells is discussed in relationship to species barrier, cell targeting, genetic susceptibility and species strain specificity. These studies further emphasize the value of the PC12 cell model system in examining the scrapie strain-host cell interaction and in addition support the concept of variation among scrapie strains.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-73-11-3027
1992-11-01
2021-10-17
Loading full text...

Full text loading...

/deliver/fulltext/jgv/73/11/JV0730113027.html?itemId=/content/journal/jgv/10.1099/0022-1317-73-11-3027&mimeType=html&fmt=ahah

References

  1. Butler D. A., Scott M. R. D., Bockman J. M., Borchelt D. R., Taraboulos A., Hsiao K. K., Kingsbury D. T., Prusiner S. B. 1988; Scrapie-infected murine neuroblastoma cells produce protease-resistant prion proteins. Journal of Virology 62:1558–1564
    [Google Scholar]
  2. Carp R. I., Rubenstein R. 1991; Diversity and significance of scrapie strains. Seminars in Virology 2:285–331
    [Google Scholar]
  3. Carp R. I., Kim Y. S., Callahan S. M. 1990; Pancreatic lesions and hypoglycemia-hyperinsulinemia in scrapie-injected hamsters. Journal of Infectious Diseases 161:462–466
    [Google Scholar]
  4. Dickinson A. G. 1976; Scrapie in sheep and goats. In Slow Virus Diseases of Animals and Man pp. 209–241 Edited by Kimberlin R. H. Amsterdam: North-Holland;
    [Google Scholar]
  5. Dickinson A. G., Bruce M. E., Fraser H., Kimberlin R. H. 1984; Scrapie strain differences: the implications of stability and mutation. In Proceedings of Workshop on Slow Transmissible Diseases pp. 105–118 Tokyo: Japanese Ministry of Health and Welfare;
    [Google Scholar]
  6. Ellman G. L., Courtney K. D., Andres V. Jr, Featherstone R. M. 1961; A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology 7:88–95
    [Google Scholar]
  7. Fonnum F. J. 1975; A rapid radiochemical method for the determination of choline acetyltransferase. Journal of Neurochemistry 24:407–409
    [Google Scholar]
  8. Gajdusek D. C. 1977; Unconventional viruses and the origin and disappearance of kuru. Science 197:943–960
    [Google Scholar]
  9. Kascsak R. J., Rubenstein R., Merz P. A., Carp R. I., Wisniewski H. M., Diringer H. 1985; Biochemical differences among scrapie-associated fibrils support the biological diversity of scrapie agents. Journal of General Virology 66:1715–1722
    [Google Scholar]
  10. Kascsak R. J., Rubenstein R., Merz P. A., Carp R. I., Robakis N. K., Wisniewski H. M., Diringer H. 1986; Immunological comparison of scrapie-associated fibrils isolated from animals infected with four different scrapie strains. Journal of Virology 59:676–683
    [Google Scholar]
  11. Kascsak R. J., Rubenstein R., Carp R. I. 1991; Evidence for biological and structural diversity among scrapie strains. Current Topics in Microbiology and Immunology 172:139–152
    [Google Scholar]
  12. Kimberlin R. H. 1979; Early events in the pathogenesis of scrapie in mice: biological and biochemical studies. In Slow Transmissible Diseases of the Nervous System vol 2 pp. 33–54 Edited by Prusiner S. B., Hadlow W. J. New York: Academic Press;
    [Google Scholar]
  13. Kimberlin R. H., Cole S., Walker C. A. 1987; Temporary and permanent modifications to a single strain of mouse scrapie on transmission to rats and hamsters. Journal of General Virology 68:1875–1881
    [Google Scholar]
  14. Kimberlin R. H., Walker C. A., Fraser H. 1989; The genomic identity of different strains of mouse scrapie is expressed in hamsters and preserved on reisolation in mice. Journal of General Virology 70:2017–2025
    [Google Scholar]
  15. Prusiner S. B., Scott M., Foster D., Pan K.-M., Groth D., Mirenda C., Torchia M., Yang S.-L., Serban D., Carlson G. A., Hoppe P. C., Westaway D., DeArmond S. J. 1990; Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63:673–686
    [Google Scholar]
  16. Race R. E., Fadness L. H., Chesebro B. 1987; Characterization of scrapie infection in mouse neuroblastoma cells. Journal of General Virology 68:1391–1399
    [Google Scholar]
  17. Race R. E., Caughey B., Graham K., Ernst D., Chesebro B. 1988; Analysis of frequency of infection, specific infectivity, and prion protein biosynthesis in scrapie-infected neuroblastoma cell clones. Journal of Virology 62:2845–2849
    [Google Scholar]
  18. Rubenstein R., Carp R. I., Callahan S. M. 1984; In vitro replication of scrapie agent in a neuronal model: infection of PC12 cells. Journal of General Virology 65:2191–2198
    [Google Scholar]
  19. Rubenstein R., Scalici C. L., Papini M. C., Callahan S. M., Carp R. I. 1990; Further characterization of scrapie replication in PC12 cells. Journal of General Virology 71:825–831
    [Google Scholar]
  20. Rubenstein R., Deng H., Scalici C. L., Papini M. C. 1991; Alterations in neurotransmitter-related enzyme activity in scrapie-infected PC12 cells. Journal of General Virology 72:1279–1285
    [Google Scholar]
  21. Scott M., Foster D., Mirenda C., Serban D., Coufal F., Wachli M., Torchia M., Groth D., Carlson G., DeArmond S. J., Westaway D., Prusiner S. B. 1989; Transgenic mice expressing hamster prion protein produce specific scrapie infectivity and amyloid plaques. Cell 59:847–857
    [Google Scholar]
  22. Waymire J. C., Bjur R., Weiner N. 1971; Assay of tyrosine hydroxylase by coupled decarboxylation of DOPA formed from 1-14C-L-tyrosine. Analytical Biochemistry 43:588–600
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-73-11-3027
Loading
/content/journal/jgv/10.1099/0022-1317-73-11-3027
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

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