1887

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Volume 67, Issue 2

Pathogenesis of Scrapie (Strain 263K) in Hamsters Infected Intracerebrally, Intraperitoneally or Intraocularly Free

Abstract

Summary

After intracerebral (i.c.) infection of hamsters, the 263K strain of scrapie replicated at a nearly constant exponential rate until clinical disease developed when titres in brain averaged 9.8 log LD i.c. units/g. After intraperitoneal infection, scrapie replication was first detected in spleen, then in thoracic spinal cord and finally in lumbar cord and brain. This pattern suggests that invasion of the central nervous system occurs by spread of infection along certain visceral autonomic nerves. Infectivity was detected in the thoracic cord only 3 to 4 weeks after infection (incubation period 16 weeks) indicating the exceptional neuroinvasiveness of this scrapie model. This observation and the failure of splenectomy to lengthen incubation period raises the possibility of direct infection of nerve tissue in the peritoneum and transport to the thoracic cord with minimal prior replication of scrapie agent extraneurally. After intraocular infection of the right eye, replication (or accumulation) of scrapie was detected in the right optic nerve and left superior colliculus, then in the right superior colliculus and finally in the left optic nerve and medulla. This pattern shows that scrapie infection can spread along nerves, possibly by intra-axonal transport. The duration of agent replication in brain (between detectable onset of replication and clinical disease) was shortest after intraperitoneal infection (51 to 58 days), longer after intracerebral infection (81 to 88 days) and longest after intraocular infection (> 121 days). These differences may reflect the relative efficiency of the neural pathways by which infectivity spreads from different sites of entry in the brain to the postulated ‘clinical target areas’.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): invasion of CNS , neural spread , pathogenesis and scrapie
© Society for General Microbiology 1986
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1986-02-01
2024-04-19
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References

  1. Al-khafazi F. A. H., Anderson P. N., Mitchell J., Mayor D. 1983; The permeability of the capsule of autonomic ganglia to horseradish peroxidase. Journal of Anatomy 134:675–682
     [Google Scholar]
  2. Bruce M. E. 1985; Agent replication dynamics in a long incubation period model of mouse scrapie. Journal of General Virology 66:2517–2522
     [Google Scholar]
  3. Buyukmihci N., Goehring-Harmon F., Marsh R. F. 1983; Neural pathogenesis of experimental scrapie after intraocular inoculation of hamsters. Experimental Neurology 81:396–406
     [Google Scholar]
  4. Chalupa L. M., Thompson I. 1980; Retinal ganglion cell projections to the superior colliculus of the hamster demonstrated by the horseradish peroxidase technique. Neuroscience Letters 19:13–19
     [Google Scholar]
  5. Clarke M. C., Haig D. A. 1971; Multiplication of scrapie agent in mouse spleen. Research in Veterinary Science 12:195–197
     [Google Scholar]
  6. Cole S., Kimberlin R. H. 1985; Pathogenesis of mouse scrapie: dynamics of vacuolation in brain and spinal cord after intraperitoneal infection. Journal of Neuropathology and Applied Neurobiology 11:213–227
     [Google Scholar]
  7. Collis S. C., Kimberlin R. H. 1985; Long term persistence of scrapie infection in mouse spleens in the absence of clinical disease. FEMS Microbiology Letters 29:111–114
     [Google Scholar]
  8. 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 vol 1 pp. 367–385 Edited by Prusiner S. B., Hadlow W. J. New York: Academic Press;
     [Google Scholar]
  9. Dickinson A. G., Outram G. W. 1979; The scrapie replication site hypothesis and its implications for pathogenesis. In Slow Transmissible Diseases of the Nervous System vol 2 pp. 13–31 Edited by Prusiner S. B. Hadlow W. J. New York: Academic Press;
     [Google Scholar]
  10. Dickinson A.G., Meikle V. M. H., Fraser H. 1969; Genetical control of the concentration of ME7 scrapie agent in the brain of mice. Journal of Comparative Pathology 79:15–22
     [Google Scholar]
  11. Diringer H. 1984; Sustained viraemia in experimental hamster scrapie. Archives of Virology 82:105–109
     [Google Scholar]
  12. 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]
  13. Ehlers B., Rudolph R., Diringer H. 1984; The reticuloendothelial system in scrapie pathogenesis. Journal of General Virology 65:423–428
     [Google Scholar]
  14. Fraser H. 1982; Neuronal spread of scrapie agent and targeting of lesions within the retino-tectal pathway. Nature, London 295:149–150
     [Google Scholar]
  15. Fraser H., Dickinson A. G. 1985; Targeting of scrapie lesions and spread of agent via the retino-tectal projection. Brain Research 346:32–41
     [Google Scholar]
  16. Haig D. A., Clarke M. C. 1965; Observations on the agent of scrapie. In Slow, Latent, and Temperate Virus Infections NINDB Monograph No 2 pp. 215–219 Edited by Gajdusek D. C. Gibbs C. J. Jr Alpers M. Washington, D.C.: U.S. Government Printing Office;
     [Google Scholar]
  17. Karber G. 1931; Beitrag zur kollectiven Behandlung pharmakologische Reihenversuche. Archives of Experimental Pathology and Pharmacology 162:480–483
     [Google Scholar]
  18. Kimberlin R. H. 1976; Experimental scrapie in the mouse: a review of an important model disease. Science Progress, Oxford 63:461–481
     [Google Scholar]
  19. 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]
  20. Kimberlin R. H., Walker C. A. 1977; Characteristics of a short incubation model of scrapie in the golden hamster. Journal of General Virology 34:295–304
     [Google Scholar]
  21. Kimberlin R. H., Walker C. A. 1978; Evidence that the transmission of one source of scrapie agent to hamsters involves separation of agent strains from a mixture. Journal of General Virology 39:487–496
     [Google Scholar]
  22. Kimberlin R. H., Walker C. A. 1979; Pathogenesis of mouse scrapie: dynamics of agent replication in spleen, spinal cord and brain after infection by different routes. Journal of Comparative Pathology 89:551–562
     [Google Scholar]
  23. Kimberlin R. H., Walker C. A. 1980; Pathogenesis of mouse scrapie: evidence for neural spread of infection to the CNS. Journal of General Virology 51:183–187
     [Google Scholar]
  24. Kimberlin R. H., Walker C. A. 1982; Pathogenesis of mouse scrapie: patterns of agent replication in different parts of the CNS following intraperitoneal infection. Journal of the Royal Society of Medicine 75:618–624
     [Google Scholar]
  25. 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 Système Nerveux Central pp. 17–33 Edited by Court L. A., Cathala F. Paris: Masson;
     [Google Scholar]
  26. Kimberlin R. H., Field H. J., Walker C. A. 1983a; Pathogenesis of mouse scrapie: evidence for spread of infection from central to peripheral nervous systems. Journal of General Virology 64:713–716
     [Google Scholar]
  27. Kimberlin R. H., Hall S. M., Walker C. A. 1983b; Pathogenesis of mouse scrapie: evidence for direct neural spread of infection to the CNS after injection of sciatic nerve. Journal of Neurological Sciences 61:315–325
     [Google Scholar]
  28. Millson G. C., Kimberlin R. H., Manning E. J., Collis S. C. 1979; Early distribution of radioactive liposomes and scrapie infectivity in mouse tissues following administration by different routes. Veterinary Microbiology 4:89–99
     [Google Scholar]
  29. Moreau-Dubois M. C., Brown P., Rohwer R. G., Masters C. L., Franko M., Gajdusek D. C. 1982; Experimental scrapie in golden Syrian hamsters: temporal comparison of in vitro cell-fusing activity with brain infectivity and histopathological changes. Infection and Immunity 37:195–199
     [Google Scholar]
  30. Pickard G. E., Silverman A. -J. 1981; Direct retinal projections to the hypothalamus, μ1riform cortex and accessory optic nuclei in the golden hamster as demonstrated by a sensitive anterograde horseradish peroxidase technique. Journal of Comparative Neurology 196:155–172
     [Google Scholar]
  31. Prusiner S. B., Groth D. F., Cochran S. P., Masiarz F. R., Mckinley M. P., Martinez H. M. 1980; Molecular properties, partial purification and assay by incubation period measurements of the hamster scrapie agent. Biochemistry 19:4883–4891
     [Google Scholar]
  32. Prusiner S. B., Cochran S. P., Groth D. F., Downey D. E., Bowman K. A., Martinez H. M. 1982; Measurement of the scrapie agent using an incubation time interval assay. Annals of Neurology 11:353–358
     [Google Scholar]
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Pathogenesis of Scrapie (Strain 263K) in Hamsters Infected Intracerebrally, Intraperitoneally or Intraocularly
J. Gen. Virol. 67, 255 (1986); https://doi.org/10.1099/0022-1317-67-2-255
/content/journal/jgv/10.1099/0022-1317-67-2-255
/content/journal/jgv/10.1099/0022-1317-67-2-255
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