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Updated: Aug 29, 2026
Assessing Transmissible Spongiform Encephalopathy Species Barriers with an In Vitro Prion Protein Conversion Assay
Published on: March 10, 2015
Susceptibility of common fibroblast cell lines to transmissible spongiform encephalopathy agents
Ina Vorberg1, Anne Raines, Brian Story
1Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. vorberg@lrz.tum.de
Abstract:
The risk of contamination of tissue culture cells with transmissible spongiform encephalopathy (TSE) agents as a result of the use of animal products as medium components has been considered to be low, in part, because only a few brain-derived cell lines have been reported to be susceptible to TSE infection. In the present study, we demonstrate that the common laboratory fibroblast cell lines NIH/3T3 and L929, which express low levels of cellular mouse prion protein, are susceptible to infection with mouse-adapted scrapie. Our results show that the susceptibility of a cell line to TSE infection cannot be predicted on the basis of its tissue origin or its level of expression of the cellular prion protein, and they suggest that any cell line expressing normal host prion protein could have the potential to support propagation of TSE agents. Thus, testing of cells for TSE susceptibility might be necessary for all cell lines that are routinely used in vaccine production and in other medical applications.
Insights
Common cell lines are susceptible to transmissible spongiform encephalopathy (TSE) agents, challenging the assumption that only brain cells can be infected. This suggests all cell lines expressing prion protein may require TSE testing for safety.
Area of Science:
- Cell biology
- Neuroscience
- Virology
Background:
- Transmissible spongiform encephalopathy (TSE) agents pose a risk to cell cultures.
- Previous understanding suggested only a few brain-derived cell lines were susceptible to TSE infection.
- The use of animal products in cell culture media raises concerns about potential contamination.
Purpose of the Study:
- To investigate the susceptibility of common laboratory fibroblast cell lines to TSE agents.
- To determine if cell lines with low prion protein expression are vulnerable to TSE infection.
- To re-evaluate the predictability of TSE susceptibility based on cell type and prion protein levels.
Main Methods:
- Infection of NIH/3T3 and L929 fibroblast cell lines with mouse-adapted scrapie.
- Monitoring of cell lines for susceptibility to TSE infection.
- Analysis of cellular prion protein expression levels in relation to infection.
Main Results:
- Common fibroblast cell lines (NIH/3T3, L929) were found to be susceptible to mouse-adapted scrapie.
- Susceptibility to TSE infection was observed even in cell lines expressing low levels of cellular prion protein.
- Cell origin and prion protein expression levels were not reliable predictors of TSE susceptibility.
Conclusions:
- Cell lines expressing normal host prion protein have the potential to propagate TSE agents.
- The susceptibility of cell lines to TSE infection cannot be solely predicted by tissue origin or prion protein expression.
- Routine TSE susceptibility testing may be necessary for all cell lines used in vaccine production and medical applications.
