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Mammalian prion propagation in PrP transgenic Drosophila

Alana M Thackray1, Olivier Andréoletti2, Raymond Bujdoso1

  • 1University of Cambridge, Department of Veterinary Medicine, Madingley Road, Cambridge, CB3 OES, UK.

Brain : a Journal of Neurology
|July 10, 2018
PubMed

Insights

Mammalian prions propagate by misfolding of cellular prion protein (PrPC) into infectious PrPSc. This study demonstrates that fruit flies (Drosophila melanogaster) can propagate mammalian prions, maintaining strain characteristics.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Infectious Diseases

Background:

  • Mammalian prions, such as those causing scrapie, propagate via template-directed misfolding of the cellular prion protein (PrPC) into abnormal PrPSc conformers.
  • Mammalian species possess co-factors essential for PrPC conformational changes and prion propagation, which may explain their susceptibility to prion diseases.

Purpose of the Study:

  • To investigate whether the invertebrate host Drosophila melanogaster, which lacks endogenous PrPC, can support the faithful propagation of mammalian prions.
  • To determine if the co-factors required for prion propagation are conserved across species or unique to mammals.

Main Methods:

  • Generation of ovine PrP transgenic Drosophila melanogaster.
  • Exposure of transgenic larvae to ovine scrapie prions.
  • Analysis of prion accumulation and biological properties in adult flies.

Main Results:

  • Transgenic Drosophila successfully accumulated transmissible prions after exposure to ovine scrapie.
  • The biological properties of distinct ovine prion strains were preserved during propagation in Drosophila.
  • This indicates that essential co-factors for prion propagation are not exclusive to mammalian hosts.

Conclusions:

  • Drosophila melanogaster can serve as a functional host for the propagation of transmissible mammalian prions.
  • The findings challenge the notion that species-specific co-factors are required for prion propagation.
  • This establishes Drosophila as a novel and powerful model system for studying mammalian prion diseases.

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