title: A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes.
abstract: Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrP(c)), into a misfolded form, abnormal PrP (PrP(Sc)), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrP(Sc) detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrP(Sc) molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrP(ARR) allele (A(136)R(154)R(171)), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.
authors.affiliation: Virologie Immunologie Moléculaires and Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Le Dur
authors.forename: Vincent
authors.initials: V
authors.lastname: Béringue
authors.forename: Olivier
authors.initials: O
authors.lastname: Andréoletti
authors.forename: Fabienne
authors.initials: F
authors.lastname: Reine
authors.forename: Thanh Lan
authors.initials: TL
authors.lastname: Laï
authors.forename: Thierry
authors.initials: T
authors.lastname: Baron
authors.forename: Bjørn
authors.initials: B
authors.lastname: Bratberg
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Vilotte
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarradin
authors.forename: Sylvie L
authors.initials: SL
authors.lastname: Benestad
authors.forename: Hubert
authors.initials: H
authors.lastname: Laude
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D005060:Europe; D005838:Genotype; D007113:Immunity, Innate / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D018620:PrPSc Proteins / Q000032:analysis / Q000472:pathogenicity*; D011328:Prions / Q000235:genetics*; D012608:Scrapie / Q000209:etiology* / Q000276:immunology / Q000635:transmission*; D012756:Sheep; D015996:Survival Rate; D014018:Tissue Distribution
chemical_list: D018620:PrPSc Proteins; D011328:Prions