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. 1986 Sep;30(3):409–413. doi: 10.1128/aac.30.3.409

Suppression of scrapie infection in mice by heteropolyanion 23, dextran sulfate, and some other polyanions.

R H Kimberlin, C A Walker
PMCID: PMC180570  PMID: 2430521

Abstract

Studies of polyanions that suppress scrapie have been done to pinpoint the cell types in the lymphoreticular system which are important in pathogenesis and to suggest possible prophylactic or therapeutic strategies for the unconventional slow viruses. A regime of three daily injections of the inorganic heteropolyanion HPA-23 reduced the effective scrapie dose by more than 99%; i.e., some mice survived peripherally injected doses of 100 50% lethal dose units. The effect was greatest when the first dose of HPA-23 was given 4 h after injecting scrapie, but it declined rapidly as this interval was increased, and there was virtually no effect 2 days after infection. A single dose of high-molecular-weight organic polyanions such as carrageenan or dextran sulfate (DS-500) greatly reduced (i.e., greater than 99%) the efficiency of scrapie infection. In contrast to HPA-23, DS-500 was equally effective whether given 4 days before or 8 h after the time of infection. The antiscrapie effect of DS-500 appeared to be independent of its activity as a B-cell mitogen and of its ability to produce a cytotoxic blockade of phagocytic cells. DS-500 probably caused the aggregation and loss from blood of scrapie inoculum which was present immediately after injection, but it had additional effects on scrapie at later times.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abraham R., Golberg L., Coulston F. Uptake and storage of degraded carrageenan in lysosomes of reticuloendothelial cells of the rhesus monkey, Macaca mulatta. Exp Mol Pathol. 1972 Aug;17(1):77–93. doi: 10.1016/0014-4800(72)90059-7. [DOI] [PubMed] [Google Scholar]
  2. Bradfield J. W. A new look at reticuloendothelial blockade. Br J Exp Pathol. 1980 Dec;61(6):617–623. [PMC free article] [PubMed] [Google Scholar]
  3. Bruce M. E. Agent replication dynamics in a long incubation period model of mouse scrapie. J Gen Virol. 1985 Dec;66(Pt 12):2517–2522. doi: 10.1099/0022-1317-66-12-2517. [DOI] [PubMed] [Google Scholar]
  4. Chermann J. C., Sinoussi F. C., Jasmin C. Inhibition of RNA-dependent DNA polymerase of murine oncornaviruses by ammonium-5-tungsto-2-antimoniate. Biochem Biophys Res Commun. 1975 Aug 18;65(4):1229–1236. doi: 10.1016/s0006-291x(75)80361-5. [DOI] [PubMed] [Google Scholar]
  5. Clarke M. C., Haig D. A. Multiplication of scrapie agent in mouse spleen. Res Vet Sci. 1971 Mar;12(2):195–197. [PubMed] [Google Scholar]
  6. Clarke M. C., Kimberlin R. H. Pathogenesis of mouse scrapie: distribution of agent in the pulp and stroma of infected spleens. Vet Microbiol. 1984 Jul;9(3):215–225. doi: 10.1016/0378-1135(84)90039-7. [DOI] [PubMed] [Google Scholar]
  7. Dickinson A. G., Fraser H., McConnell I., Outram G. W. Mitogenic stimulation of the host enhances susceptibility to scrapie. Nature. 1978 Mar 2;272(5648):54–55. doi: 10.1038/272054a0. [DOI] [PubMed] [Google Scholar]
  8. Dickinson A. G., Fraser H. Scrapie: effect of Dh gene on incubation period of extraneurally injected agent. Heredity (Edinb) 1972 Aug;29(1):91–93. doi: 10.1038/hdy.1972.67. [DOI] [PubMed] [Google Scholar]
  9. Ehlers B., Diringer H. Dextran sulphate 500 delays and prevents mouse scrapie by impairment of agent replication in spleen. J Gen Virol. 1984 Aug;65(Pt 8):1325–1330. doi: 10.1099/0022-1317-65-8-1325. [DOI] [PubMed] [Google Scholar]
  10. Ehlers B., Rudolph R., Diringer H. The reticuloendothelial system in scrapie pathogenesis. J Gen Virol. 1984 Feb;65(Pt 2):423–428. doi: 10.1099/0022-1317-65-2-423. [DOI] [PubMed] [Google Scholar]
  11. Farquhar C. F., Dickinson A. G. Prolongation of scrapie incubation period by an injection of dextran sulphate 500 within the month before or after infection. J Gen Virol. 1986 Mar;67(Pt 3):463–473. doi: 10.1099/0022-1317-67-3-463. [DOI] [PubMed] [Google Scholar]
  12. Fischer J., Ricard L., Weiss R. The structure of the heteropolytungstate (NH4)17Na NaW21Sb9O86-14H2O. An inorganic crypate. J Am Chem Soc. 1976 May 12;98(10):3050–3052. doi: 10.1021/ja00426a081. [DOI] [PubMed] [Google Scholar]
  13. Fowler E. F., Thomson A. W. Effect of carrageenan on activity of the mononuclear phagocyte system in the mouse. Br J Exp Pathol. 1978 Apr;59(2):213–219. [PMC free article] [PubMed] [Google Scholar]
  14. Fraser H., Dickinson A. G. Pathogenesis of scrapie in the mouse: the role of the spleen. Nature. 1970 May 2;226(5244):462–463. doi: 10.1038/226462a0. [DOI] [PubMed] [Google Scholar]
  15. Fraser H., Dickinson A. G. Studies of the lymphoreticular system in the pathogenesis of scrapie: the role of spleen and thymus. J Comp Pathol. 1978 Oct;88(4):563–573. doi: 10.1016/0021-9975(78)90010-5. [DOI] [PubMed] [Google Scholar]
  16. Jasmin C., Chermann J. C., Herve G., Teze A., Souchay P., Boy-Loustau C., Raybaud N., Sinoussi F., Raynaud M. In vivo inhibition of murine leukemia and sarcoma viruses by the heteropolyanion 5-tungsto-2-antimoniate. J Natl Cancer Inst. 1974 Aug;53(2):469–474. doi: 10.1093/jnci/53.2.469. [DOI] [PubMed] [Google Scholar]
  17. Kasper K. C., Stites D. P., Bowman K. A., Panitch H., Prusiner S. B. Immunological studies of scrapie infection. J Neuroimmunol. 1982 Nov;3(3):187–201. doi: 10.1016/0165-5728(82)90022-4. [DOI] [PubMed] [Google Scholar]
  18. Kimberlin R. H., Hall S. M., Walker C. A. Pathogenesis of mouse scrapie. Evidence for direct neural spread of infection to the CNS after injection of sciatic nerve. J Neurol Sci. 1983 Oct-Nov;61(3):315–325. doi: 10.1016/0022-510x(83)90165-x. [DOI] [PubMed] [Google Scholar]
  19. Kimberlin R. H. Scrapie: how much do we really understand? Neuropathol Appl Neurobiol. 1986 Mar-Apr;12(2):131–147. doi: 10.1111/j.1365-2990.1986.tb00046.x. [DOI] [PubMed] [Google Scholar]
  20. Kimberlin R. H., Walker C. A. Antiviral compound effective against experimental scrapie. Lancet. 1979 Sep 15;2(8142):591–592. doi: 10.1016/s0140-6736(79)91654-4. [DOI] [PubMed] [Google Scholar]
  21. Kimberlin R. H., Walker C. A. Pathogenesis of mouse scrapie: dynamics of agent replication in spleen, spinal cord and brain after infection by different routes. J Comp Pathol. 1979 Oct;89(4):551–562. doi: 10.1016/0021-9975(79)90046-x. [DOI] [PubMed] [Google Scholar]
  22. Kimberlin R. H., Walker C. A. The antiviral compound HPA-23 can prevent scrapie when administered at the time of infection. Arch Virol. 1983;78(1-2):9–18. doi: 10.1007/BF01310854. [DOI] [PubMed] [Google Scholar]
  23. Larnicol N., Augery Y., Le Bousse-Kerdiles C., Degiorgis V., Chermann J. C., Teze A., Jasmin C. In vivo effect of a new mineral condensed ion (HPA 39) on murine Friend leukaemia. J Gen Virol. 1981 Jul;55(Pt 1):17–23. doi: 10.1099/0022-1317-55-1-17. [DOI] [PubMed] [Google Scholar]
  24. Marsh R. F. Effect of vaccinia-activated macrophages on scrapie infection in hamsters. Adv Exp Med Biol. 1981;134:359–363. doi: 10.1007/978-1-4757-0495-2_32. [DOI] [PubMed] [Google Scholar]
  25. McFarlin D. E., Raff M. C., Simpson E., Nehlsen S. H. Scrapie in immunologically deficient mice. Nature. 1971 Oct 1;233(5318):336–336. doi: 10.1038/233336a0. [DOI] [PubMed] [Google Scholar]
  26. Outram G. W., Dickinson A. G., Fraser H. Reduced susceptibility to scrapie in mice after steroid administration. Nature. 1974 Jun 28;249(460):855–856. doi: 10.1038/249855a0. [DOI] [PubMed] [Google Scholar]
  27. Outram G. W., Dickinson A. G., Fraser H. Slow encephalopathies, inflammatory responses and arachis oil. Lancet. 1975 Jan 25;1(7900):198–200. doi: 10.1016/s0140-6736(75)91363-x. [DOI] [PubMed] [Google Scholar]
  28. Outram G. W. The pathogenesis of scrapie in mice. Front Biol. 1976;44:325–357. [PubMed] [Google Scholar]
  29. Rubenstein R., Carp R. I., Callahan S. M. In vitro replication of scrapie agent in a neuronal model: infection of PC12 cells. J Gen Virol. 1984 Dec;65(Pt 12):2191–2198. doi: 10.1099/0022-1317-65-12-2191. [DOI] [PubMed] [Google Scholar]
  30. Souhami R. L., Bradfield J. W. The recovery of hepatic phagocytosis after blockade of Kupffer cells. J Reticuloendothel Soc. 1974 Aug;16(2):75–86. [PubMed] [Google Scholar]
  31. Turner E. V., Higginbotham R. D. Effects of intravenous carrageenan on immune responses and on the reticulonendothelial system. J Reticuloendothel Soc. 1979 Dec;26(6):763–773. [PubMed] [Google Scholar]
  32. Worthington M., Clark R. Lack of effect of immunosuppression on scrapie infection in mice. J Gen Virol. 1971 Nov;13(2):349–351. doi: 10.1099/0022-1317-13-2-349. [DOI] [PubMed] [Google Scholar]

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