vCJD prion acquires altered virulence through trans-species infection

Masahiro Asano1, Shirou Mohri, James W Ironside

  • 1Division of CJD Science and Technology, Department of Prion Research, Center for Translational and Advanced Animal Research on Human Diseases, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba, Sendai 980-8575, Japan.

Insights

Variant Creutzfeldt-Jakob disease (vCJD) transmission was studied in mice with humanized PrP genes. Human heterozygotes at codon 129 may be susceptible to vCJD, indicating a risk for secondary infections.

Area of Science:

  • Neuroscience
  • Prion Diseases
  • Genetics

Background:

  • Variant Creutzfeldt-Jakob disease (vCJD) is linked to bovine spongiform encephalopathy (BSE) prions.
  • All vCJD patients identified to date are homozygous for methionine at codon 129 of the PrP gene.

Purpose of the Study:

  • To investigate the influence of codon 129 polymorphism on susceptibility to BSE and vCJD prions.
  • To assess the risk of vCJD infection in individuals with different PrP genotypes.

Main Methods:

  • Utilized humanized knock-in mice expressing human PrP transgenes.
  • Infected mice peripherally and assessed prion susceptibility using splenic follicular dendritic cell assays and Western blotting.

Main Results:

  • Humanized mice showed low susceptibility to BSE prions, with only Met/Met homozygotes exhibiting weak susceptibility.
  • vCJD prions were transmitted to humanized mice with Met/Met and Met/Val genotypes.
  • Mice with Val/Val genotype were not susceptible to vCJD prions.

Conclusions:

  • Codon 129 polymorphism significantly impacts susceptibility to vCJD prions.
  • Human heterozygotes (Met/Val) at codon 129 are susceptible to vCJD, suggesting a risk for secondary transmission.

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