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UMR INRA-ENVT, Physiopathologie Infectieuse et Parasitaire des Ruminants, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France1
INRA, Laboratoire de Pathologie Infectieuse et Immunologie, F-37380 Nouzilly, France2
INRA, Virologie et Immunologie Moléculaires, Jouy-en-Josas, France3
Department of Immunology, Pathobiology and Epidemiology, Institute for Animal Science and Health (ID-Lelystad), Lelystad, The Netherlands4
INRA, Station d’Amélioration Génétique des Animaux, Auzeville, France5
Author for correspondence: Patricia Berthon. Fax +33 2 47 42 77 79. e-mail berthon{at}tours.inra.fr
The immune system is known to be involved in the early phase of scrapie pathogenesis. However, the infection route of naturally occurring scrapie and its spread within the host are not entirely known. In this study, the pathogenesis of scrapie was investigated in sheep of three PrP genotypes, from 2 to 9 months of age, which were born and raised together in a naturally scrapie-affected Romanov flock. The kinetics of PrPSc accumulation in sheep organs were determined by immunohistochemistry. PrPSc was detected only in susceptible VRQ/VRQ sheep, from 2 months of age, with an apparent entry site at the ileal Peyer’s patch as well as its draining mesenteric lymph node. At the cellular level, PrPSc deposits were associated with CD68-positive cells of the dome area and B follicles before being detected in follicular dendritic cells. In 3- to 6-month-old sheep, PrPSc was detected in most of the gut-associated lymphoid tissues (GALT) and to a lesser extent in more systemic lymphoid formations such as the spleen or the mediastinal lymph node. All secondary lymphoid organs showed a similar intensity of PrPSc-immunolabelling at 9 months of age. At this time-point, PrPSc was also detected in the autonomic myenteric nervous plexus and in the nucleus parasympathicus nervi X of the brain stem. These data suggest that natural scrapie infection occurs by the oral route via infection of the Peyer’s patches followed by replication in the GALT. It may then spread to the central nervous system through the autonomic nervous fibres innervating the digestive tract.
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O. Andreoletti, C. Lacroux, A. Chabert, L. Monnereau, G. Tabouret, F. Lantier, P. Berthon, F. Eychenne, S. Lafond-Benestad, J.-M. Elsen, et al. PrPSc accumulation in placentas of ewes exposed to natural scrapie: influence of foetal PrP genotype and effect on ewe-to-lamb transmission J. Gen. Virol., October 1, 2002; 83(10): 2607 - 2616. [Abstract] [Full Text] [PDF]
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 W. Tuo, K. I. O'Rourke, D. Zhuang, W. P. Cheevers, T. R. Spraker, and D. P. Knowles Pregnancy status and fetal prion genetics determine PrPSc accumulation in placentomes of scrapie-infected sheep PNAS, April 30, 2002; 99(9): 6310 - 6315. [Abstract] [Full Text] [PDF]
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N. A. Mabbott, G. McGovern, M. Jeffrey, and M. E. Bruce Temporary Blockade of the Tumor Necrosis Factor Receptor Signaling Pathway Impedes the Spread of Scrapie to the Brain J. Virol., April 16, 2002; 76(10): 5131 - 5139. [Abstract] [Full Text] [PDF]
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R. Heggebo, C. McL. Press, G. Gunnes, L. Gonzalez, and M. Jeffrey Distribution and accumulation of PrP in gut-associated and peripheral lymphoid tissue of scrapie-affected Suffolk sheep J. Gen. Virol., February 1, 2002; 83(2): 479 - 489. [Abstract] [Full Text] [PDF]
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M. Moudjou, Y. Frobert, J. Grassi, and C. La Bonnardiere Cellular prion protein status in sheep: tissue-specific biochemical signatures J. Gen. Virol., August 1, 2001; 82(8): 2017 - 2024. [Abstract] [Full Text] [PDF]
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