Skip to main content
SpringerLink
Log in

Amphotericin B treatment dissociates in vivo replication of the scrapie agent from PrP accumulation

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

SCRAPIE and related animal and human disorders are neurodegenerative diseases1 characterized by the formation of a modified, partly proteinase-resistant protein (PrP) of the host2,3,which tends to aggregate as amyloid fibrils4 and accumulate in the brain of infected individuals5. There is a general consensus that the pathological form of PrP (PrPSc) is essential for the clinical appearance of the disease6, but whether it is part of the scrapie agent7 or a by-product of viral infection8,9is still controversial. Here we report that treatment of scrapie-infected hamsters with amphotericin B delays the accumulation in the brain of the proteinase-resistant portion of PrPSc by about 30 days without affecting scrapie replication. The consequence is that hamsters treated with amphotericin B developed clinical signs of disease later than infected controls. We argue that the proteinase-resistant portion of PrPSc is necessary for the development of the disease but that it is unlikely to be essential for scrapie replication.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gajdusek, D. C. in Virology (eds Fields, B. N. & Knipe, D. M.) 2289–2324 (Raven, New York, 1990).

    Google Scholar 

  2. Oesch, B. et al. Cell 40, 735–746 (1985).

    Article  CAS  Google Scholar 

  3. Chesebro, B. et al. Nature 315, 331–333 (1985).

    Article  ADS  CAS  Google Scholar 

  4. Prusiner, S. B. et al. Cell 35, 349–358 (1983).

    Article  CAS  Google Scholar 

  5. McKinley, M. P., Bolton, D. C. & Prusiner, S. B. Cell 35, 57–62 (1983).

    Article  CAS  Google Scholar 

  6. Brunori, M., Silvestrini, M. C. & Pocchiari, M. Trends biochem. Sci. 13, 309–313 (1988).

    Article  CAS  Google Scholar 

  7. Prusiner, S. B. Science 252, 1515–1522 (1991).

    Article  ADS  CAS  Google Scholar 

  8. Braig, H. R. & Diringer, H. EMBO J. 4, 2300–2309 (1985).

    Article  Google Scholar 

  9. Manuelidis, L., Sklaviadis, T. & Manuelidis, E. E. EMBO J. 6, 341–347 (1987).

    Article  CAS  Google Scholar 

  10. Pocchiari, M., Schmittinger, S. & Masullo, C. J. gen. Virol. 68, 219–223 (1987).

    Article  CAS  Google Scholar 

  11. Casaccia, P. et al. Antimicrob. Agents Chemother. 35, 1486–1488 (1991).

    Article  CAS  Google Scholar 

  12. Pocchiari, M., Casaccia, P. & Ladogana, A. J. infect. Dis. 160, 795–802 (1989).

    Article  CAS  Google Scholar 

  13. Kimberlin, R. H., Walke, C. A. & Fraser, H. J. gen. Virol. 70, 2017–2025 (1989).

    Article  Google Scholar 

  14. Diringer, H. et al. Nature 306, 476–478 (1983).

    Article  ADS  CAS  Google Scholar 

  15. Motulsky, H. J. & Ransnas, L. A. FASEB J. 1, 365–374 (1987).

    Article  CAS  Google Scholar 

  16. Reed, J. & Muench, H. Am. J. Hyg. 27, 493–497 (1938).

    Google Scholar 

  17. Prusiner, S. B. et al. Biochemistry 19, 4883–4891 (1980).

    Article  CAS  Google Scholar 

  18. Hope, J., Multhaup, G., Reekie, L. J. D., Kimberlin, R. H. & Beyreuther, K. Eur. J. Biochem. 172, 271–277 (1988).

    Article  CAS  Google Scholar 

  19. Medoff, G., Brajtburg, J., Kobayashi, G. S. & Bolard, J. A. Rev. Pharmac. Toxicol. 23, 303–330 (1983).

    Article  CAS  Google Scholar 

  20. Dickinson, A. G. & Outram, G. W. Ciba Fdn Symp. 135, 209–223 (1988).

    Google Scholar 

  21. Weissmann, C. Nature 352, 679–683 (1991).

    Article  ADS  CAS  Google Scholar 

  22. Kimberlin, R. H. & Walker, C. A. J. gen. Virol. 34, 295–304 (1977).

    Article  CAS  Google Scholar 

  23. Kimberlin, R. H., Cole, S. & Walker, C. A. J. gen. Virol. 68, 1875–1881 (1987).

    Article  Google Scholar 

  24. Dickinson, A. G. in Slow Virus Diseases of Animals and Man (ed. Kimberlin, R. H.) 209–241 (North Holland, Amsterdam, 1976).

    Google Scholar 

  25. Pocchiari, M. & Masullo, C. in Neurologia e Scienze di Base (eds Gainotti, G., Bentivoglio, M., Bergonzi, P. & Ferro, F. M.) 571–582 (Vita e Pensiero, Milano, 1989).

    Google Scholar 

  26. De Lean, A., Munson, P. J. & Rodbard, D. Am. J. Physiol. 235, E97–E102 (1978).

    Article  CAS  Google Scholar 

  27. Hilmert, H. & Diringer, H. Biosci. Rep. 4, 165–170 (1984).

    Article  CAS  Google Scholar 

  28. Kascsak, R. J. et al. J. Virol. 59, 676–683 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Laemmli, U. K. Nature 227, 680–685 (1970).

    Article  ADS  CAS  Google Scholar 

  30. Towbin, H., Staehelin, T. & Gorden, J. Proc. natn. Acad. Sci. U.S.A. 76, 4350–4354 (1979).

    Article  ADS  CAS  Google Scholar 

  31. Casaccia, P., Ladogana, A., Masullo, C., Macchi, G. & Pocchiari, M. in Trends Neuroimmun. (eds Marrosu, M. G., Cianchetti, C. & Tavolato, B.) 135–149 (Plenum, New York, 1990).

    Book  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Istituto di Patologia Generate, Università Cattolica S. Cuore, Largo F. Vito 1, 00168, Rome, Italy

    You Geng Xi, Loredana Ingrosso, Anna Ladogana, Carlo Masullo & Maurizio Pocchiari

  2. Istituto di Neurologia, Università Cattolica S. Cuore, Largo F. Vito 1, 00168, Rome, Italy

    Carlo Masullo

  3. Laboratorio di Virologia, Istituto Superiore di Sanita, Rome, Italy

    Maurizio Pocchiari

Authors
  1. You Geng Xi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Loredana Ingrosso
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anna Ladogana
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carlo Masullo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maurizio Pocchiari
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xi, Y., Ingrosso, L., Ladogana, A. et al. Amphotericin B treatment dissociates in vivo replication of the scrapie agent from PrP accumulation. Nature 356, 598–601 (1992). https://doi.org/10.1038/356598a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/356598a0

  • Springer Nature Limited

This article is cited by

Search

Navigation