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Updated: Dec 16, 2025
Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster
Published on: March 12, 2018
Prion infection, transmission, and cytopathology modeled in a low-biohazard human cell line
Merve Avar1, Daniel Heinzer1, Nicolas Steinke1
1Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
Abstract:
Transmission of prion infectivity to susceptible murine cell lines has simplified prion titration assays and has greatly reduced the need for animal experimentation. However, murine cell models suffer from technical and biological constraints. Human cell lines might be more useful, but they are much more biohazardous and are often poorly infectible. Here, we describe the human clonal cell line hovS, which lacks the human PRNP gene and expresses instead the ovine PRNP VRQ allele. HovS cells were highly susceptible to the PG127 strain of sheep-derived murine prions, reaching up to 90% infected cells in any given culture and were maintained in a continuous infected state for at least 14 passages. Infected hovS cells produced proteinase K-resistant prion protein (PrPSc), pelletable PrP aggregates, and bona fide infectious prions capable of infecting further generations of naïve hovS cells and mice expressing the VRQ allelic variant of ovine PrPC Infection in hovS led to prominent cytopathic vacuolation akin to the spongiform changes observed in individuals suffering from prion diseases. In addition to expanding the toolbox for prion research to human experimental genetics, the hovS cell line provides a human-derived system that does not require human prions. Hence, the manipulation of scrapie-infected hovS cells may present fewer biosafety hazards than that of genuine human prions.
Insights
A novel human cell line, hovS, efficiently replicates sheep prions, offering a safer and more effective model for studying prion diseases and reducing animal use in research.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Murine cell lines simplify prion research but have limitations.
- Human cell lines are desirable but pose higher biosafety risks and are often less susceptible to infection.
- Developing a human-derived cell model for prion studies is crucial.
Purpose of the Study:
- To develop and characterize a human clonal cell line susceptible to prion infection.
- To create a safer experimental system for prion research that avoids the use of infectious human prions.
Main Methods:
- Genetically engineered human cells (hovS) lacking the human PRNP gene but expressing the ovine PRNP VRQ allele.
- Infection of hovS cells with a sheep-derived prion strain (PG127).
- Analysis of prion protein (PrPSc) formation, aggregation, infectivity, and cytopathic effects.
Main Results:
- The hovS cell line demonstrated high susceptibility to PG127 prions, reaching up to 90% infection rates.
- Infected hovS cells maintained prion infectivity for at least 14 passages and produced PrPSc and infectious prions.
- Infection induced vacuolation, mimicking spongiform changes seen in prion diseases.
- Infected hovS cells successfully infected other naïve hovS cells and mice expressing ovine PrP.
- The hovS system provides a human-derived model for prion research without requiring infectious human prions.
Conclusions:
- The hovS cell line is a highly susceptible human-derived model for studying sheep prions.
- This cell line offers a valuable tool for prion research, potentially reducing biosafety hazards associated with human prions.
- hovS expands the available models for prion disease research and human experimental genetics.
