Mouse-adapted sporadic human Creutzfeldt-Jakob disease prions propagate in cell culture
Related Experiment Video
Updated: Jul 4, 2026
Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster
Published on: March 12, 2018
Victoria A Lawson1, Laura J Vella, James D Stewart
1Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Abstract:
Cell based models used for the study of prion diseases have traditionally employed mouse-adapted strains of sheep scrapie prions. To date, attempts to generate human prion propagation in cell culture have been unsuccessful. Rabbit kidney epithelial cells (RK13) are permissive to infection with prions from a variety of species upon expression of cognate PrP transgenes. We explored RK13 cells expressing human PrP for their utility as a cell line capable of sustaining infection with human prions. RK13 cells processed exogenously expressed human PrP similarly to exogenously expressed mouse PrP but were not permissive to infection when exposed to sporadic Creutzfeldt-Jakob disease prions. Transmission of the same sporadic Creutzfeldt Jakob disease prions to wild-type mice generated a strain of mouse-adapted human prions, which efficiently propagated in RK13 cells expressing mouse PrP, demonstrating these cells are permissive to infection by mouse-adapted human prions. Our observations underscore the likelihood that, in contrast to prions derived from non-human mammals, additional unidentified cofactors or subcellular environment are critical for the generation of human prions.
Insights
Generating human prions in cell culture remains challenging. Rabbit kidney epithelial cells expressing human PrP did not propagate human prions, suggesting cofactors are needed for human prion generation.
Area of Science:
- Neuroscience
- Cell Biology
- Infectious Diseases
Background:
- Cell-based models are crucial for studying prion diseases.
- Traditionally, mouse-adapted scrapie strains are used, but human prion propagation in vitro has been unsuccessful.
Purpose of the Study:
- To investigate the utility of rabbit kidney epithelial (RK13) cells expressing human PrP for sustained human prion infection.
- To understand barriers to human prion propagation in cell culture.
Main Methods:
- RK13 cells expressing human PrP were exposed to sporadic Creutzfeldt-Jakob disease (sCJD) prions.
- The same sCJD prions were adapted to mice, and the resulting mouse-adapted human prions were used to infect RK13 cells expressing mouse PrP.
Main Results:
- RK13 cells expressing human PrP did not support propagation of sCJD prions.
- RK13 cells expressing mouse PrP efficiently propagated mouse-adapted human prions.
- Exogenous human PrP processing in RK13 cells mimicked that of mouse PrP.
Conclusions:
- RK13 cells are not permissive to direct human prion infection.
- Propagation of mouse-adapted human prions in RK13 cells indicates cellular permissiveness to specific prion strains.
- Additional cofactors or specific subcellular environments may be essential for human prion generation in vitro.
