Summary
In most experimental models of scrapie and in some naturally infected species, the lymphoreticular system and the spleen in particular play a major role in the pathogenesis of the disease. Previous studies demonstrated scrapie infectivity in peripheral organs from the day of infection up to the terminal stage. The discovery of the abnormal prion protein, PrPres, as a specific molecular hallmark of scrapie should permit enhanced study of scrapie pathogenesis and has some pharmacological applications. In this study, PrPres accumulation was followed day by day in peripheral organs. Four different phases were identified: the circulation of scrapie inoculum, a clearance phase, the peripheral accumulation of PrPres and a plateau phase. This kinetics was then pharmacologically modified (i) by applying the macrophage “suicide” technique to unveil the cellular types involved in scrapie pathogenesis and (ii) with anti-scrapie drugs such as polyene antibiotics, polyanions and Congo red to investigate their mode and site of action.
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References
Adjou KT, Deslys JP, Pemaimay R, Seman M, Dormont D (1998) Prospects for the pharmacological treatment of human prion diseases. CNS Drugs 10: 83–89
Aguzzi A (2000) Prion diseases, blood and the immune system: concerns and reality. Haematologica 85: 3–10
Beringue V, Demaimay R, Adjou KT, Demart S, Lamoury F, Seman M, Lasmézas CI, Deslys JP, Dormont D (1998) Polyene antibiotics in experimental transmissible subacute spongiform encephalopathies, In: Morrison DRO (ed) Prions and brain diseases in animals and humans. Plenum Press, New York, pp 177–185
Beringue V, Lasmézas CI, Adjou KT, Demaimay R, Lamoury F, Deslys JP, Seman M, Dormont D (1999) Inhibiting scrapie neuroinvasion by polyene antibiotic treatment of SCID mice. J Gen Virol 80: 1873–1877
Beringue V, Demoy M, Lasmézas CI, Gouritin B, Weingarten C, Deslys JP, Andreux JP, Couvreur P, Dormont D (2000) Role of spleen macrophages in the clearance of scrapie agent early in the pathogenesis. J Pathol 190: 495–502
Beringue V, Adjou KT, Lamoury F, Maignien T, Deslys JP, Race R, Dormont D (2000) Opposite effects of dextran sulfate 500, the polyene antibiotic MS-8209 and Congo red on accumulation of the protease-resistant isoform of PrP in the spleens of mice inoculated intraperitoneally with the scrapie agent. J Virol 74: 5432–5440
Brown KL, Stewart K, Ritchie DL, Mabbott NA, Williams A, Fraser H, Morrison WI, Bruce ME (1999) Scrapie replication in lymphoid tissues depends on prion protein-expressing follicular dendritic cells. Nature Med 5: 1308–1312
Carp RI, Callahan SM (1982) Effect of mouse peritoneal macrophages on scrapie infectivity during extended in vitro incubation. Intervirology 17: 201–207
Caspi S, Halimi M, Yanai A, BenSasson S, Taraboulos A, Gabizon R (1998) The anti-prion activity of Congo red. Putative mechanism. J Biol Chem 273: 3484–3489
Caughey B, Race RE (1992) Potent inhibition of scrapie-associated PrP accumulation by Congo Red. J Neurochem 59: 768–771
Caughey B, Brown K, Raymond GJ, Katenstein GE, Thresher W (1994) Binding of thp protease-sensitive form of prion protein PrP to sulfated glycosaminoglycan and Congo red. J Virol 68: 2135–2141
Claassen I, Van Rooijen N, Claaseen E (1990) A new method for removal of mononuclear phagocytes from heterogeneous cell populations in vitro, using the liposome-mediated macrophage “suicide” technique. J Immunol Methods 134: 153–161
Collinge J (1999) Variant Creutzfeldt-Jakob disease. Lancet 354: 317–323
Demaimay R, Adjou KT, Beringue V, Demart S, Lasmézas CI, Deslys JP, Seman M, Dormont D (1997) Late treatment with polyene antibiotics can prolong the survival time of scrapie-infected animals. J Virol 71: 9685–9689
Demaimay R, Race R, Chesebro B (1999) Effectiveness of polyene antibiotics in treatment of transmissible spongiform encephalopathy in transgenic mice expressing Syrian hamster PrP only in neurons. J Virol 73: 3511–3513
Ingrosso L, Ladogana A, Pocchiari M (1995) Congo red prolongs the incubation period in scrapie-infected hamsters. J Virol 69: 506–508
Kimberlin RH, Walker CA (1988) Pathogenesis of experimental scrapie. Ciba Found Symposium 135: 37–62
Lasmézas CI, Deslys JP, Robain O, Jaegly A, Beringue V, Peyrin JM, Fournier JG, Hauw JJ, Rossier J, Dormont D (1997) Transmission of the BSE agent to mice in the absence of detectable abnormal prion protein. Science 275: 402–405
Mabbott NA, Farquhar CF, Brown KL, Bruce ME (1998) Involvement of the immune system in TSE pathogenesis. Immunol Today 19: 201–203
Maignien T, Lasmézas CI, Beringue V, Dormont D, Deslys JP (1999) Pathogenesis of the oral route of infection of mice with scrapie and bovine spongiform encephalopathy agents. J Gen Virol 80: 3035–3042
Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216: 136–144
Prusiner SB, McKinley MP, Bowman KA, Bolton DC, Bendheim PE, Groth DF, Glenner GG (1983) Scrapie prions aggregate to form amyloid-like birefringent rods. Cell 35: 349–358
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Beringue, V. et al. (2000). Pharmacological manipulation of early PrPres accumulation in the spleen of scrapie-infected mice. In: Groschup, M.H., Kretzschmar, H.A. (eds) Prion Diseases. Archives of Virology. Supplementa, vol 16. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6308-5_4
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DOI: https://doi.org/10.1007/978-3-7091-6308-5_4
Publisher Name: Springer, Vienna
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