1887

Abstract

Amphotericin B (AmB) has been shown to delay hamster scrapie. Infectivity studies have been performed previously using AmB in order to understand the relationship between the accumulation of an abnormal isoform (PrPres) of the prion protein and 263K scrapie agent replication in the brain. The first study reported that AmB had no effect upon agent replication, although it delayed the development of both clinical signs and PrPres accumulation. However, subsequent experiments using the same model showed a significant effect both on agent replication and PrPres accumulation early in infection. This fundamental discrepancy was assumed to be linked to differences in experimental protocols. In order to unravel the issue, a new experiment has been performed encompassing different protocols and using an AmB derivative, MS-8209, that can be used at higher doses because of its lower toxicity. The findings of this study exclude the suspected differences in the protocols as the reason for previous conflicting results, and suggest strongly that these discrepancies were due to a low dose of AmB causing a ‘threshold effect’. Overall, this study indicates that, in this model, PrPres cannot be dissociated from infectivity by polyene antibiotics.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-80-4-1079
1999-04-01
2022-09-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/80/4/0801079a.html?itemId=/content/journal/jgv/10.1099/0022-1317-80-4-1079&mimeType=html&fmt=ahah

References

  1. Adjou K. T., Demaimay R., Lasmézas C., Deslys J. P., Seman M., Dormont D. 1995; MS-8209, a new amphotericin B derivative, provides enhanced efficacy in delaying hamster scrapie. Antimicrobial Agents and Chemotherapy 39:2810–2812
    [Google Scholar]
  2. Adjou K. T., Demaimay R., Lasmézas C. I., Seman M., Deslys J. P., Dormont D. 1996; Differential effects of a new amphotericin B derivative, MS-8209, on mouse BSE and scrapie: implications for the mechanism of action of polyene antibiotics. Research in Virology 147:213–218
    [Google Scholar]
  3. Adjou K. T., Deslys J.-P., Demaimay R., Dormont D. 1997; Probing the dynamics of prion diseases with amphotericin B. Trends in Microbiology 5:27–31
    [Google Scholar]
  4. Adjou K. T., Deslys J. P., Demaimay R., Seman M., Dormont D. 1998; Prospects for the pharmacological treatment of human prion diseases. CNS Drugs 10:83–89
    [Google Scholar]
  5. Amyx H., Salazar A. M., Gajdusek D. C., Gibbs C. J. 1984; Chemotherapeutic trials in experimental slow virus disease. Neurology 34: (Suppl.) 149
    [Google Scholar]
  6. 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]
  7. Brown P. 1990; A therapeutic panorama of the spongiform encephalopathies. Antiviral Chemistry & Chemotherapy 1:75–83
    [Google Scholar]
  8. Caughey B., Chesebro B. 1997; Prion protein and the transmissible spongiform encephalopathies. Trends in Cell Biology 7:56–62
    [Google Scholar]
  9. Demaimay R., Adjou K., Lasmézas C., Lazarini F., Cherifi K., Seman M., Deslys J.-P., Dormont D. 1994; Pharmacological studies of a new derivative of amphotericin B, MS-8209, in mouse and hamster scrapie. Journal of General Virology 75:2499–2503
    [Google Scholar]
  10. Demaimay R., Adjou K. T., Beringue V., Demart S., Lasmézas C. I., Deslys J.-P., Seman M., Dormont D. 1997; Late treatment with polyene antibiotics can prolong the survival time of scrapie-infected animals. Journal of Virology 71:9685–9689
    [Google Scholar]
  11. Diringer H., Ehlers B. 1991; Chemoprophylaxis of scrapie in mice. Journal of General Virology 72:457–460
    [Google Scholar]
  12. Dormont D., Delpech B., Delpech A., Courcel M. N., Viret J., Markovits P., Court L. 1981; Hyperproduction de protéine gliofibrillaire acide (GFAP) au cours de l′ évolution de la tremblante expérimentale de la souris. Comptes Rendus de l’Académic des Sciences de Paris 293:53–56
    [Google Scholar]
  13. Ehlers B., Diringer H. 1984; Dextran sulphate 500 delays and prevents mouse scrapie by impairment of agent replication in spleen. Journal of General Virology 65:1325–1330
    [Google Scholar]
  14. Georgsson G., Gisladottir E., Arnadottir S. 1993; Quantitative assessment of the astrocytic response in natural scrapie of sheep. Journal of Comparative Pathology 108:229–240
    [Google Scholar]
  15. Hill A. F., Desbruslais M., Joiner S., Sidle K. C. L., Gowland I., Collinge J., Doey L. J., Lantos P. 1997; The same prion strain causes vCJD and BSE. Nature 389:448–450
    [Google Scholar]
  16. Ingrosso L., Ladogana A., Pocchiari M. 1995; Congo red prolongs the incubation period in scrapie–infected hamsters. Journal of Virology 69:506–508
    [Google Scholar]
  17. Kimberlin R. H., Walker C. A. 1983; The antiviral compound HPA– 23 can prevent scrapie when administered at the time of infection. Archives of Virology 78:9–18
    [Google Scholar]
  18. Kimberlin R. H., Walker C. A. 1986; Suppression of scrapie infection in mice by heteropolyanion 23, dextran sulfate, and some other polyanions. Antimicrobial Agents and Chemotherapy 30:409–413
    [Google Scholar]
  19. Ladogana A., Casaccia P., Ingrosso L., Cibati M., Salvatore M., Xi Y.-G., Masullo C., Pocchiari M. 1992; Sulphate polyanions prolong the incubation period of scrapie-infected hamsters. Journal of General Virology 73:661–665
    [Google Scholar]
  20. Lasmézas C. I., Deslys J. P., Robain O., Jaegly A., Beringue V., Peyrin J. M., Fournier J. G., Hauw J. J., Rossier J., Dormont D. 1997; Transmission of the BSE agent to mice in the absence of detectable abnormal prion protein. Science 275:402–405
    [Google Scholar]
  21. Lazarini F., Boussin F., Deslys J. P., Tardy M., Dormont D. 1994; Astrocyte gene expression in experimental mouse scrapie. Journal of Comparative Pathology 111:87–98
    [Google Scholar]
  22. Mackenzie A. 1983; Immunohistochemical demonstration of glial fibrillary acidic protein in scrapie. Journal of Comparative Pathology 93:251–259
    [Google Scholar]
  23. McKenzie D., Kaczkowski J., Marsh R., Aiken J. 1994; Amphotericin B delays both scrapie agent replication and PrP-res accumulation early in infection. Journal of Virology 68:7534–7536
    [Google Scholar]
  24. Manuelidis L., Fritch W., Xi Y. G. 1997; Evolution of a strain of CJD that induces BSE-like plaques. Science 277:94–98
    [Google Scholar]
  25. Manuelidis L., Fritch W., Zaitsev I. 1998; Dapsone to delay symptoms in Creutzfeldt–Jakob disease. Lancet 352:456
    [Google Scholar]
  26. Medoff G., Brajtburg J., Kobayashi G. S., Bolard J. 1983; Antifungal agents useful in therapy of systemic fungal infections. Annual Review of Pharmacology and Toxicology 23:303–330
    [Google Scholar]
  27. Merz P. A., Somerville R. A., Wisniewski H. M., Manuelidis L., Manuelidis E. E. 1983; Scrapie–associated fibrils in Creutzfeldt–Jakob disease. Nature 306:474–476
    [Google Scholar]
  28. Pocchiari M., Schmittinger S., Masullo C. 1987; Amphotericin B delays the incubation period of scrapie in intracerebrally inoculated hamsters. Journal of General Virology 68:219–223
    [Google Scholar]
  29. Pocchiari M., Casaccia P., Ladogana A. 1989a; Amphotericin B: a novel class of antiscrapie drugs. Journal of Infectious Diseases 160:795–802
    [Google Scholar]
  30. Pocchiari M., Schmittinger S., Ladogana A., Masullo C. 1989b; Effects of amphotericin B in intracerebrally scrapie inoculated hamsters. In Unconventional Virus Diseases of the Central Nervous System pp 314–323 Edited by Dormont D., Court L. A., Brown P., Kingsbury D. T. Fontenay aux Roses: CEA Diffusion;
    [Google Scholar]
  31. Pocchiari M., Ingrosso L., Cardone F., Ladogana A., Eleni C., Agrimi U. 1996; Effect of amphotericin B on 263K and 139H strains of scrapie in Armenian hamsters. In Transmissible Subacute Spongiform Encephalopathies: Prion Diseases pp 185–190 Edited by Court L., Dodet B. Paris: Elsevier;
    [Google Scholar]
  32. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144
    [Google Scholar]
  33. Prusiner S. B. 1992; Chemistry and biology of prions. Biochemistry 31:12277–12288
    [Google Scholar]
  34. Reed L. J., Muench H. 1938; A simple method of estimating fifty percent endpoints. American Journal of Hygiene 27:493–496
    [Google Scholar]
  35. Saint Julien L., Joly V., Seman M., Carbon C., Yeni P. 1992; Activity of MS–8209, a nonester amphotericin B derivative, in treatment of experimental systemic mycoses. Antimicrobial Agents and Chemotherapy 36:2722–2728
    [Google Scholar]
  36. Somerville R. A., Dunn A. J. 1996; The association between PrP and infectivity in scrapie and BSE infected mouse brain. Archives of Virology 141:275–289
    [Google Scholar]
  37. Tagliavini F., McArthur R. A., Canciani B., Giaccone G., Porro M., Bugiani M., Lievens P. M.-J., Bugiani O., Peri E., Dall’Ara P., Rocchi M., Poli G., Forloni G., Bandiera T., Varasi M., Suarato A., Cassutti P., Cervini M. A., Lansen J., Salmona M., Post C. 1997; Effectiveness of anthracycline against experimental prion disease in Syrian hamsters. Science 276:1119–1122
    [Google Scholar]
  38. Weissmann C. 1991; Spongiform encephalopathies. The prion′s progress. Nature 349:569–571
    [Google Scholar]
  39. Xi Y. G., Ingrosso L., Ladogana A., Masullo C., Pocchiari M. 1992; Amphotericin B treatment dissociates in vivo replication of the scrapie agent from PrP accumulation. Nature 356598–601
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-80-4-1079
Loading
/content/journal/jgv/10.1099/0022-1317-80-4-1079
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