NR ATFF
AU Lasmezas,C.I.; Herzog,C.; Sales,N.; Lescoutra-Etchegaray,N.; Riviere,J.; Deslys,J.P.
TI Pathogenesis of CJD in Non Human Primates
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Oral sessions ORAL-10
PT Konferenz-Vortrag
AB
The occurrence of variant Creutzfeldt-Jakob Disease (vCJD) linked to human contamination with the BSE agent has posed a new challenge to medical authorities in charge of protecting human health against iatrogenic disease transmission. The context of uncertainty regarding the number of vCJD patients including two blood transfusion-related secondary cases, as well as the exact pathogenesis of the infection, render risk assessments very difficult.
Sporadic CJD (sCJD) can be transmitted between humans through medical procedures including highly infected organs like the central nervous system. However, in variant CJD (vCJD), lymphoreticular tissue also harbors PrPtse. The recent observation of small amounts of PrPtse in spleen and muscle in sCJD raised the possibility that peripheral PrPtse is not limited to vCJD cases.
We aimed to clarify the peripheral pathogenesis of human TSEs by using a non-human primate model. A highly sensitive ELISA was adapted to the detection of extraneural PrPtse. We show that organs can be divided into two categories with respect to their PrPtse content. The first is restricted to the lymphoreticular organs in the vCJD/BSE model, which accumulate high amounts of PrPtse, and thus could be considered to represent a high risk of iatrogenic transmission. The second corresponds to several organs with low amounts of PrPtse associated with nervous structures found in the sporadic, iatrogenic and variant CJD models. In contrast to the first set of organs, this low level of tissue contamination is not strain-restricted and seems to be linked to secondary centrifugal spread of the agent through nerves. This study rationally dissects the tissue specific versus general tropism of prion strains in primates and provides an additional experimental basis for the classification of human organs into different risk categories.
IN Die Autoren fanden erhebliche TSE-Infektiosität relativ früh nach der Inokulation in lymphoiden Organen CJK-infizierter Makaken nur dann, wenn die Empfängertiere mit vCJK oder BSE infiziert wurden. Auch bei mit sCJK infizierten Empfängertieren fanden sie eine allerdings wesentlich geringere Infektiosität relativ lange nach der Inokulation in verschiedenen peripheren Organen an den Stellen ihrer Innervierung. Während die starke primäre Infektiosität in ihrem System Erregerstamm-spezifisch auftritt, erfolgt die sekundäre Ausbreitung von Prionen aus dem Zentralnervensystem in periphere Organe erregerstammunabhängig. Uneingeschränkt übertragbar ist dieses Modell aber wohl nicht, denn in Schafen findet man bei jedem Erregerstamm eine Beteiligung des lymphoretikulären Systems.
AD C.I.Lasmézas, Scripps Florida, Department of Infectiology, 5353 Parkside Drive, RF-2, Jupiter, 33458 Florida, USA; C.Herzog, N.Salès, N.Lescoutra-Etchegaray, J.Rivière, J.P.Deslys, CEA, Départment de Recherche Médicinale, 18, route du Panorame, 92265 Fontenay-aux-Roses, France
SP englisch
PO Deutschland