Variant Creutzfeldt-Jakob Disease strain is identical in individuals of two PRNP codon 129 genotypes

Abigail Diack, Aileen Boyle, Christopher Plinston, Emma Hunt, Matthew Bishop, Robert Will, Jean Manson

Research output: Contribution to journalArticlepeer-review

Abstract

In 2004, a sub-clinical case of variant Creutzfeldt-Jakob Disease in a PRNP 129 methionine/valine heterozygous individual infected via blood transfusion was reported and we established that the spleen from this individual was infectious. Since host genetics is an important factor in strain modification, the identification of variant Creutzfeldt-Jakob Disease infection in a PRNP 129 methionine/valine heterozygous individual has raised the possibility that the properties of the variant Creutzfeldt-Jakob Disease agent could change after transmission to this different genetic background and concerns that this could lead to a more virulent strain of variant Creutzfeldt-Jakob Disease. The variant Creutzfeldt-Jakob Disease strain has to date been characterised only in methionine homozygous individuals therefore to establish whether the strain characteristics of variant Creutzfeldt-Jakob Disease had been modified by the host genotype, spleen material with PrP deposition from a PRNP 129 methionine/valine individual was inoculated into a panel of wildtype mice. Three passages in mice were undertaken to allow stabilisation of the strain characteristics following its passage into mice. In each passage, a combination of clinical signs, neuropathology (Transmissible Spongiform Encephalopathy vacuolation and PrP deposition) were analysed and biochemical analysis carried out. While some differences were observed at primary and first subpassage, following the second subpassage, strain characteristics in the methionine/valine individual were totally consistent with those of variant Creutzfeldt-Jakob Disease transmitted to 129 methionine/valine individuals thus demonstrated no alteration in strain properties were imposed by passage through the different host genotype. Thus we have demonstrated variant Creutzfeldt-Jakob Disease strain properties are not affected by transmission through an individual with the PRNP methionine/valine codon 129 genotype and thus no alteration in virulence should be associated with the different host genotype.
Original languageEnglish
Pages (from-to)1416-1428
JournalBrain
Volume142
Issue number5
DOIs
Publication statusPublished - 1 Apr 2019

Keywords

  • Variant Creutzfeldt-Jakob Disease
  • Prion
  • PRNP
  • transmissible spongiform encephalopathy

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