Prion Protein Expression and Processing in Human Mononuclear Cells: The Impact of the Codon 129 Prion Gene Polymorphism

Christiane Segarra,Joliette Coste,Sylvain Lehmann,Adam J Ratner

doi:10.1371/journal.pone.0005796

Abstract

BackgroundSo 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 FindingsWe 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/SignificanceThese 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.

Highlights

Transmissible spongiform encephalophathies (TSEs or prion diseases) are fatal neurodegenerative disorders, of which the main human form is Creutzfeldt–Jakob disease (CJD) [1,2]
Conclusions/Significance: These results suggest that in peripheral blood mononuclear cells (PBMCs), the M129V PrP polymorphism has no significant impact on PrP expression, processing and the apparent glycoform distribution
One possible mechanism explaining the relationship between the M129V polymorphism and disease development, would be that the polymorphism influences PrPC expression and processing critical for prion propagation [4,16,17,35]

Summary

Introduction

Transmissible spongiform encephalophathies (TSEs or prion diseases) are fatal neurodegenerative disorders, of which the main human form is Creutzfeldt–Jakob disease (CJD) [1,2]. In order to investigate a possible relationship between the M129V polymorphism and susceptibility to vCJD and PrPC expression, we compared three blood donor populations of different genotypes: M/M, M/V, and V/V at position 129. We analyzed their expression of total PrPC (mRNA, protein) and PrPC isoforms (glycosylated and truncated proteins) in peripheral blood mononuclear cells (PBMCs).

Results

Conclusion