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Studies on the alimentary pathogensis of BSE agent and natural scrapie in sheep and mice. Implications for diagnosis and control *

Contract nr: QLRT-CT-2000-02332
Project type: RS (Research and Technological Development Project)
Starting date:
Duration: 48 months
Total cost: 1,927,534 EUR
EC Contribution: 1,368,742 EUR
Scientific Officer:
Research topic: 5.1.1. Sustainable agriculture/Animal Systems

Abstract:
This project will study the early pathogenesis of scrapie and bovine spongiform encephalopathy (BSE) in sheep and mice, with emphasis on the uptake and accumulation of the prion protein (PrP) and infectivity in the gut-associated and peripheral lymphoid tissues and its relevance to neuroinvasion. The transport of PrP across the mucosa of the gut and the interaction of disease-associated PrP with leukocytes, FDCs and nerves will be studied in novel systems such as isolated intestinal loops, surgical micro-infection, B-cell depleted sheep, and transgenic mice overexpressing ovine PrP. The consequences of accumulation of PrP in lymphoid tissues for neuroinvasion and the development of a carrier state will be assessed. A better understanding of the early pathogenesis of scrapie and BSE in sheep will contribute to the detection of the pre-clinical disease and in developing future control and eradication strategies.

Objectives:
This project will study the early pathogenesis of scrapie and BSE in sheep and mice, with emphasis on the uptake and accumulation of the prion protein (PrP) and infectivity in the gut-associated and peripheral lymphoid tissues and its relevance to neuroinvasion. The objectives of the project are to:

1. Investigate the role of mucosal transport systems and the involvement of gut-associated lymphoid tissues in the uptake and passage of scrapie and BSE across the intestinal mucosa.
2. Study key cellular events in peripheral lymphoid tissues related to the establishment of scrapie and BSE infection and their influence on neuroinvasion, immunomorphology and infectivity.
3. Evaluate the implications of early peripheral pathogenesis of scrapie and BSE for the carrier state and control strategies.

 


Coordinator
Jon TEIGE
Norwegian School of Veterinary Science
Oslo
NORWAY
Tel.: +47 22964500
Fax: +47 224764
E-mail: Jon.Teige@veths.no


Partners
  Geoff WOOD
Ministry of Agriculture Fisheries And Food
Addlestone
UNITED KINGDOM
Tel.: +44 01932357894
Fax: +44 01932357230
E-mail: gwood@vla.maff.gsi.gov.uk
  Hans DE VRIES
Department of immunology, pathology and epidemiology
Lelystad
THE NETHERLANDS
Tel.: +31 320238238
Fax: +31 320238238
E-mail: h.w.devries@id.wag-ur.nl
  Thomas C. METTENLEITER
Federal Research Centre for Virus Diseases of Animals, Prion Group Institute for Immunology
Tübingen
GERMANY
Tel.: +49 383517250
Fax: +49 383517151
E-mail: mettenleiter@rie.bfav.de