Infectious prions accumulate to high levels in non proliferative C2C12 myotubes

• Published in: PLoS pathogens 2013-11, Vol.9 (11), p.e1003755-e1003755
• Main Authors: Herbst, Allen, Banser, Pamela, Velasquez, Camilo Duque, Mays, Charles E, Sim, Valerie L, Westaway, David, Aiken, Judd M, McKenzie, Debbie
• Format: Article
• Language: English
• Subjects: Animals; Cell division; Cell Line; Cell Proliferation; Colleges & universities; Creutzfeldt-Jakob disease; Cricetinae; Dilution; Gene expression; Health aspects; Mammals; Mice; Muscle cells; Muscle Fibers, Skeletal; Physiological aspects; Prions; PrPSc Proteins - metabolism; Rodents; Species Specificity
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003755

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.