Infectious Prions Accumulate to High Levels in Non Proliferative C2C12 Myotubes

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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.

Vyšlo v časopise: Infectious Prions Accumulate to High Levels in Non Proliferative C2C12 Myotubes. PLoS Pathog 9(11): e32767. doi:10.1371/journal.ppat.1003755
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003755

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