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J. Virol. doi:10.1128/JVI.01454-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Molecular and transmission characteristics of primary passaged ovine scrapie isolates in conventional and ovine PrP transgenic mice

Centre for Veterinary Science, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 OES, UK; Neuropathology Unit, Department of Pathology, Veterinary Laboratories, Agency, Weybridge, New Haw, Addlestone, Surrey KT15 3NB, UK

^* To whom correspondence should be addressed. Email: rb202{at}cam.ac.uk.

	Abstract

A more complete assessment of ovine prion strain diversity will be achieved by complementing biological strain typing in conventional and ovine PrP transgenic mice with a biochemical analysis of the resultant PrPSc. This will provide a correlation between ovine prion strain phenotype and the molecular nature of different PrP conformers associated with particular prion strains. Here, we have compared the molecular and transmission characteristics of ovine ARQ/ARQ and VRQ/VRQ scrapie isolates following primary passage in tg338 (VRQ) and tg59 (ARQ) ovine PrP transgenic mice and the conventional mouse lines C57BL/6, RIII (both Prnp^a) and VM (Prnp^b). Our data show that these different genotypes of scrapie isolates display similar incubation periods of >350 days in conventional and tg59 mice. Facilitated transmission of sheep scrapie isolates occurred in tg338 mice with incubation times for VRQ/VRQ inocula reduced to 64 days, and to 210 days for ARQ/ARQ samples. Distinct genotype-specific lesion profiles were seen in the brains of conventional and tg59 prion-diseased mice, which was accompanied by the accumulation of more conformationally stable PrPSc, following inoculation with ARQ/ARQ compared to VRQ/VRQ scrapie isolates. In contrast, the lesion profiles, quantities and stability of PrPSc induced by the same inocula in tg338 mice were more similar than in the other mouse lines. Our data show that primary transmission of different genotypes of ovine prions is associated with the formation of different conformers of PrPSc with distinct molecular properties and provides the basis of a molecular approach to identify the true diversity of ovine prion strains.