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Updated: Feb 15, 2026
Assessing Transmissible Spongiform Encephalopathy Species Barriers with an In Vitro Prion Protein Conversion Assay
Published on: March 10, 2015
Behind the potential evolution towards prion resistant species
Natalia Fernández-Borges1, Hasier Eraña1, Joaquín Castilla1,2
1a CIC bioGUNE, Parque Tecnológico de Bizkaia , Derio , Spain.
Abstract:
Historically, the observation of naturally occurring cases of prion disease led to the classification of different susceptibility grades and to the designation of prion resistant species. However, the development of highly efficient in vitro prion propagation systems and the generation of ad hoc transgenic models allowed determining that leporidae and equidae families have been erroneously considered resistant to prion infection. On the contrary, similar approaches revealed an unexpected high level of resistance of the canidae family. In PLoS Pathogens [ 1 ], we describe experiments directed toward elucidating which are the determinants of the alleged prion resistance of this family. Studies based on the sequence of the canine prion protein coupled with structural in silico analysis identified a key residue probably implicated in this resistance. Cell and brain-based PMCA highlighted that the presence of aspartic or glutamic acid at codon 163 of the canid PrP, strongly inhibits prion replication in vitro. Transgenic animals carrying this substitution in mouse PrP were resistant to prion infection after intracerebral challenge with different mouse prion strains. The confirmation of the importance of this substitution and its exclusivity in this family, suggests it could have been evolutionarily favored, due to their diet based on carrion and small ruminants.
Insights
Canine prion protein (PrP) resistance to prion disease is linked to a specific amino acid at codon 163. This finding explains why dogs are resistant to prion infections and has implications for understanding prion disease evolution.
Area of Science:
- Neuroscience
- Molecular Biology
- Veterinary Science
Background:
- Prion diseases are transmissible neurodegenerative disorders.
- Species susceptibility to prion diseases has been historically classified, but in vitro and transgenic models have refined this understanding.
- The Canidae family exhibits unexpected resistance to prion infections.
Purpose of the Study:
- To investigate the molecular determinants of prion resistance in the Canidae family.
- To identify specific residues in the canine prion protein (PrP) responsible for this resistance.
Main Methods:
- Sequence analysis of canine PrP.
- In silico structural analysis.
- Cell-free prion replication assays (PMCA).
- Generation and testing of transgenic mouse models.
Main Results:
- A specific amino acid substitution (aspartic or glutamic acid) at codon 163 of the canid PrP was identified as a key factor inhibiting prion replication in vitro.
- Transgenic mice expressing this canine PrP substitution were resistant to infection with various mouse prion strains.
- This protective substitution appears to be exclusive to the Canidae family.
Conclusions:
- The presence of aspartic or glutamic acid at codon 163 of canid PrP is a major determinant of resistance to prion infection.
- This resistance mechanism may have been evolutionarily selected in canids due to their diet.
- Understanding species-specific resistance can inform prion disease research and management.
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