Infectious Prions Accumulate to High Levels in Non Proliferative C2C12 Myotubes

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.