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Allelic Interference in Prion Replication Is Modulated by the Convertibility of the Interfering PrPC and Other

Juan Carlos Espinosa1, Olivier Andreoletti2, Alba Marín-Moreno1

  • 1Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.

Mbio
|March 17, 2021
PubMed

Insights

Prion protein (PrPC) coexpression in transgenic mice can interfere with prion disease, depending on the prion strain. Interference is reduced if the second PrPC is efficiently converted, but murine PrPSc propagation is favored.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Prion protein (PrPC) coexpression in transgenic models influences prion propagation.
  • The phenomenon of
  • interference
  • in prion disease requires further elucidation.

Purpose of the Study:

  • To investigate prion propagation in mice coexpressing PrPC from two different species.
  • To determine how simultaneous PrPC expression affects prion infection and propagation.

Main Methods:

  • Crossbreeding transgenic mouse lines to generate mice coexpressing bovine/porcine, bovine/murine, or murine/porcine PrPC.
  • Inoculating these mice and hemizygous controls with various prion strains from cattle, mice, and pigs.

Main Results:

  • Observed interference with prion infection, indicated by extended survival times and reduced attack rates.
  • Interference was diminished when the interfering PrPC species was efficiently converted by the prion strain.
  • Propagation of endogenous murine PrPSc was favored, suggesting a role for host factors.

Conclusions:

  • Coexpression of a second prion protein (PrPC) can interfere with prion propagation in a strain-dependent manner.
  • The effectiveness of interference correlates with the transmissibility of the prion in the host expressing only the interfering PrPC.
  • Host-specific factors beyond PrP amino acid sequence may influence prion interference.
Keywords:
BSEprion interferenceprion propagationprion replicationprion strainscrapie

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