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Published on: August 8, 2017
Prion protein expression and processing in human mononuclear cells: the impact of the codon 129 prion gene
Christiane Segarra1, Sylvain Lehmann, Joliette Coste
1Etablissement Français du Sang de Pyrénées Méditerranée, Montpellier, France.
Background:
So far, all clinical cases of new variant Creutzfeldt-Jakob disease (vCJD), thought to result from the Bovine Spongiform Encephalopathy (BSE) prion agent, have shown Methionine-Methionine (M/M) homozygosity at the M129V polymorphism of the PRNP gene. Although established, this relationship is still not understood. In both vCJD and experimental BSE models prion agents do reach the bloodstream, raising concerns regarding disease transmission through blood transfusion.
Methodology/Principal Findings:
We investigated the impact of the M129V polymorphism on the expression and processing of the prion protein in human peripheral blood mononuclear cells (PBMCs) from three blood donor populations with Methionine-Methionine (M/M), Valine-Valine (V/V) and M/V genotypes. Using real-time PCR, ELISA and immunoblot assays we were unable to find differences in prion protein expression and processing relating to the M129V polymorphism.
Conclusions/Significance:
These results suggest that in PBMCs, the M129V PrP polymorphism has no significant impact on PrP expression, processing and the apparent glycoform distribution. Prion propagation should be investigated further in other cell types or tissues.
Insights
The M129V PRNP gene polymorphism does not affect prion protein expression or processing in human peripheral blood mononuclear cells (PBMCs). Further research is needed in other tissues to understand prion propagation.
Area of Science:
- Neuroscience
- Genetics
- Infectious Diseases
Background:
- Variant Creutzfeldt-Jakob disease (vCJD) cases are linked to M/M homozygosity at the PRNP gene's M129V polymorphism.
- Prion agents are found in the bloodstream, raising concerns about transfusion-transmitted vCJD.
- The mechanism behind the M129V polymorphism's influence on vCJD remains unclear.
Purpose of the Study:
- To investigate the impact of the M129V polymorphism on prion protein (PrP) expression and processing.
- To analyze PrP in human peripheral blood mononuclear cells (PBMCs) across different M129V genotypes (M/M, V/V, M/V).
Main Methods:
- Real-time PCR, ELISA, and immunoblot assays were used.
- PBMCs from three blood donor populations representing M/M, V/V, and M/V genotypes were analyzed.
Main Results:
- No significant differences in PrP expression were observed concerning the M129V polymorphism.
- PrP processing and apparent glycoform distribution showed no significant variation across genotypes.
- The M129V polymorphism did not impact PrP levels or modification in PBMCs.
Conclusions:
- The M129V PRNP gene polymorphism does not significantly influence PrP expression or processing in human PBMCs.
- These findings suggest that other cell types or tissues may be more relevant for studying prion propagation related to this polymorphism.
- Further investigation into prion propagation mechanisms in different cellular contexts is warranted.
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