NR ATFB
AU Laude,H.
TI Prion Diversity in Small Ruminants
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Oral sessions ORAL-06
PT Konferenz-Vortrag
AB
Serial transmission to inbred mouse lines where characteristics of incubation time and brain vacuolation give different patterns is the current way for investigating strain diversity in sheep scrapie. Development of the disease commonly requires 1-2 years upon primary transmission, and a notable proportion of isolates fail to transmit. Consequently, a limited number of isolates have been studied yet, and the extent of natural scrapie strain variation remains largely unexplored. In the aim to improve the feasibility of such studies, we have examined the susceptibility of transgenic mice expressing the VRQ allele of ovine PrP.
Mice of the high expressor line tg338 have been inoculated with more than 60 scrapie sources including sheep from various geographical areas and of distinct PrP genotypes, and a few goats. Remarkably, all isolates transmitted disease with an overall ~ 100 % attack rate. The incubation time differed widely among isolates, with 50 % of them transmitting within 200 days post-IC inoculation. The isolates were found to distribute in 5 distinct groups according to the brain PrPsc distribution pattern and the survival time on subpassage. Importantly, all differed from experimental sheep BSE agent transmitted to the same mice, the sole exception being a goat isolate identified through random screening.
The intensified surveillance of scrapie in Europe together with the improvement of PrPsc detection techniques have led to the discovery of a growing number of so-called atypical cases. Inoculation to tg338 mice of 10 samples that produced discordant responses in rapid tests applied to screening of slaughtered or fallen animals showed that such cases were associated with a truly, highly infectious TSE agent. Its characteristics were closely similar to that of Nor98 agent. Worryingly, this agent appears to be capable of infecting sheep with genotypes naturally conferring resistance to scrapie.
Altogether these data show that PrPVRQ tg mice represent a promising tool for investigating ruminant TSE diversity and evolution.
TL Laï, F Reine, A Laisné, A Le Dur, V Beringue (VIM), N Chesnais, J Costa, M Hudrisier, JL Vilotte (LGBC), M Pilot (UEAR), from INRA-Jouy, have contributed to these studies. Many other colleagues have to be acknowledged for their collaboration and/or the supply of scrapie isolates : U Agrimi, O Andreoletti, T Baron, S Benestad, M Dawson, M Eloit (chair of the French Typing Network), J Grassi, M Groschup, N Hunter, L van Keulen, E Monk, P Sarradin, JM Torres.
IN
Der Autor berichtet allein über die Arbeit vieler Kollegen, die mehr als 60 Scrapie-Isolate von Schafen und wenigen Ziegen vermutlich zumindest hauptsächlich in Frankreich sammelten und damit intracerebral Mäuse inokulierten, die das VRQ-Allel des Schafprionproteins überexprimierten und praktisch alle erkrankten. Anhand der Inkubationszeiten bei den primären Übertragungen und nachfolgenden Passagen sowie anhand der Verteilung des PrPsc im Gehirn ließen sich die Scrapie-Isolate in 5 Gruppen einteilen, die sich alle - mit Ausnahme einer Scrapie-kranken Ziege - von BSE in Schafen unterschieden.
Etwa die Hälfte der Isolate führten in der primären Übertragungen zu Inkubationszeiten unter 200 Tagen.
Diese speziellen Empfängermäuse wurden auch für 10 Isolate sogenannter diskordanter Scrapiefälle eingesetzt, die aufgrund reduzierter Proteinase-K-Resistenz nur mit dem Schnetttest von BioRad erkannt wurden. Auch diese Scrapie-Fälle erwiesen sich in diesem System als infektiös und ähnelten hinsichtlich der oben genannten Merkmale Nor98-Fällen.
AD H.Laude, Unité Virologie Immunologie Moléculaires, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France
SP englisch
PO Deutschland