NR AOVN
AU Lasmezas,C.I.; Herzog,C.; Etchegaray,N.; Dormont,D.; Deslys,J.P.
TI Pathogenesis of BSE in non-human primates
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Oral sessions OS-04
PT Konferenz-Vortrag
AB
Variant Creutzfeldt-Jakob disease (vCJD) is an acquired human prion disease due to contamination by the BSE agent. In this disease, the abnormal isoform of the prion protein (PrPres) can be found in peripheral tissues including spleen, tonsils and appendix. This stands in contrast to other human TSEs (like sporadic CJD) and is a recognized risk as a source of iatrogenic spread. However, extensive studies on the peripheral pathogenesis of the BSE agent in human beings are not possible. Today, vCJD / BSE infection of Cynomologus macaques provides the closest model to humans that reliably reproduces vCJD.1,2
We investigated the body distribution of PrPres in Cynomologus monkeys infected by different prion strains and inoculation routes. We show that in vCJD infected animals PrPres is present not only in lymphoid tissues but also in discrete portions of the gastrointestinal tract. This finding was specific to animals inoculated with vCJD or BSE (when compared to iCJD or sCJD animals). Furthermore, among vCJD / BSE infected monkeys, the distribution and amount of PrPres in different organs varied depending on the inoculation route (oral, intravenous, intracerebral). Thus, in addition to strain specific properties, the inoculation route also contributes to determine the spread of the agent in the organism.
However, the sciatic nerve seems not to abide by the same rule, as it was found positive in all tested animals. The presence of PrPres in this tissue appears not to be strain / inoculation route restricted.
These data provide insight into the complex role of strains and infectious routes for the peripheral pathogenesis of human TSEs and will further be useful to define guidelines to avoid interhuman contamination by surgical procedures.
1. Lasmézas C.I., et al. BSE transmission to macaques. Nature 1996;381: 743-744.
2. Lasmézas C.I., et al.. Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt-Jakob Disease: Implications for human health. Proc Natl Acad Sci USA 2001 ; 98, 4142-4147.
AD C. Lasmézas, C. Herzog, N. Etchegaray, D. Dormont, J-P Deslys, CEA, Départment de Recherche, France
SP englisch
PO Deutschland