Mammalian prion propagation in PrP transgenic Drosophila.

Abstract

Mammalian prions propagate by template-directed misfolding and aggregation of normal cellular prion related protein PrPC 28 as it converts into disease-associated conformers collectively referred to as PrPSc 29 . Mammalian species may be permissive for prion disease because these hosts have co-evolved specific co-factors that assist PrPC 30 conformational 31 change and prion propagation. We have tested this hypothesis by examining whether faithful prion propagation occurs in the normally PrPC 32 -null invertebrate host Drosophila 33 melanogaster. Ovine PrP transgenic Drosophila exposed at the larval stage to ovine scrapie 34 showed a progressive accumulation of transmissible prions in adult flies. Strikingly, the 35 biological properties of distinct ovine prion strains were maintained during their propagation 36 in Drosophila. Our observations show that the co-factors necessary for strain-specific prion 37 propagation are not unique to mammalian species. Our studies establish Drosophila as a 38 novel host for the study of transmissible mammalian prions.