Infectious Prions Accumulate to High Levels in Non Proliferative C2C12 Myotubes

PLoS Pathogens

Valerie L. Sim¹  Camilo Duque Velasquez¹  Allen Herbst¹  Judd M. Aiken¹  Pamela Banser²  David Westaway²  Charles E. Mays³  Debbie McKenzie⁴ 

[1] Centre 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;Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada;Division of Neuroscience, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

关键词: Prions;    Animal prion diseases;    Prion diseases;    Myoblasts;    Cell cultures;    Muscle differentiation;    Gene expression;    Hamsters;   

DOI  :  10.1371/journal.ppat.1003755

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Prion diseases are driven by the strain-specific, template-dependent transconformation of the normal cellular prion protein (PrPC) into a disease specific isoform PrPSc. 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 PrPSc 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 PrPSc and that the level of infectivity produced in these post-mitotic cells, 105.5 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.

【 授权许可】

CC BY