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Updated: May 5, 2026
Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
Infectious prions accumulate to high levels in non proliferative C2C12 myotubes
Allen Herbst1, Pamela Banser, Camilo Duque Velasquez
1Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada ; Department of Agriculture, Food and Nutritional Sciences, University of Alberta, Edmonton, Alberta, Canada.
Abstract:
Prion diseases are driven by the strain-specific, template-dependent transconformation of the normal cellular prion protein (PrP(C)) into a disease specific isoform PrP(Sc). Cell culture models of prion infection generally use replicating cells resulting in lower levels of prion accumulation compared to animals. Using non-replicating cells allows the accumulation of higher levels of PrP(Sc) and, thus, greater amounts of infectivity. Here, we infect non-proliferating muscle fiber myotube cultures prepared from differentiated myoblasts. We demonstrate that prion-infected myotubes generate substantial amounts of PrP(Sc) and that the level of infectivity produced in these post-mitotic cells, 10(5.5) L.D.50/mg of total protein, approaches that observed in vivo. Exposure of the myotubes to different mouse-adapted agents demonstrates strain-specific replication of infectious agents. Mouse-derived myotubes could not be infected with hamster prions suggesting that the species barrier effect is intact. We suggest that non-proliferating myotubes will be a valuable model system for generating infectious prions and for screening compounds for anti-prion activity.
Insights
Non-replicating muscle myotubes efficiently accumulate high levels of infectious prions (PrP(Sc)), approaching in vivo levels. This novel model system is valuable for studying prion diseases and screening anti-prion compounds.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Prion diseases involve the misfolding of cellular prion protein (PrP(C)) into infectious PrP(Sc).
- Traditional cell culture models yield low prion accumulation, limiting their utility.
- Non-replicating cells offer a potential for higher prion levels and infectivity.
Purpose of the Study:
- To investigate the utility of non-proliferating muscle myotubes as a model for prion infection.
- To quantify PrP(Sc) accumulation and infectivity in these cells.
- To assess prion strain specificity and species barrier effects in myotubes.
Main Methods:
- Differentiated myoblasts were cultured into non-proliferating myotubes.
- Myotubes were infected with mouse-adapted prion agents.
- PrP(Sc) levels and infectivity (L.D.50/mg) were measured.
- Infection with different prion strains and species was tested.
Main Results:
- Prion-infected myotubes generated substantial PrP(Sc) and high infectivity levels (10(5.5) L.D.50/mg).
- Myotubes demonstrated strain-specific prion replication.
- Mouse myotubes were resistant to hamster prions, indicating an intact species barrier.
Conclusions:
- Non-proliferating myotubes are a robust model for generating infectious prions.
- This model system can be used for screening anti-prion drug candidates.
- Myotube cultures provide valuable insights into prion disease mechanisms.
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