No Adaptation of the Prion Strain in a Heterozygous Case of Variant Creutzfeldt-Jakob Disease

Abstract

We investigated a clinical case of variant Creutzfeldt-Jakob Disease in a person heterozygous for methionine/valine at codon 129 of the prion protein gene and identified the same strain properties in variant Creutzfeldt-Jakob disease in methionine homozygous persons and in bovine spongiform encephalopathy. These results indicate no adaptation of the agent in a different genetic background.

Keywords: Bovine spongiform encephalopathy; prions and related diseases; strain; transmissible spongiform encephalopathy; vCJD; variant Creutzfeldt-Jakob disease; zoonoses.

Figure 1

Vacuolation profiles of a clinical case of vCJD in a prion protein gene codon 129MV individual, pooled data from UK 129MM cases (n = 7) and pooled data from UK bovine spongiform encephalopathy cases (n = 8) show similarities in vacuolar pathology intensity and distribution in wild-type mouse brains. Data show mean ± SEM of clinical and pathological positive mice (n≥6 per group). G1–G9, gray matter scoring regions: G1, medulla; G2, cerebellum; G3, superior colliculus; G4, hypothalamus; G5, thalamus; G6, hippocampus; G7, septum; G8, retrosplenial and adjacent motor cortex; G9, cingulate and adjacent motor cortex. W1–W3, white matter scoring regions: W1, cerebellar white matter; W2, mesencephalic tegmentum; W3, cerebral peduncle. MM, methionine homozygous; MV, methionine/valine; vCJD, variant Creutzfeldt-Jakob disease.

Figure 2

Neuropathology of RIII mice inoculated with material from a clinical case of vCJD in a prion protein gene codon 129MV individual, a typical 129MM case of vCJD, and BSE. A, B) Haemotoxylin and Eosin staining of transmissible spongiform encephalopathy vacuolation in the cochlear nucleus of mice inoculated with material from a clinical 129MV case (arrows). C–E) Abnormal PrP deposition in the cerebellum of mice inoculated with C) clinical 129MV case, D) typical 129MM case, and E) BSE. F–H) Abnormal PrP deposition in the hippocampus of mice inoculated with samples of F) clinical 129MV case, G) typical 129MM case, and H) BSE. I–K) Abnormal PrP deposition in the CA2 region of the hippocampus; I) inset from panel F; J) inset from panel G; K) inset from panel H. Monoclonal antibody: 6H4. Scale bars: A–B, F–H: 200 µm. C–E, I–K: 100 µm. BSE, bovine spongiform encephalopathy; MM, methionine homozygous; MV, methionine/valine; PrP, prion protein; vCJD, variant Creutzfeldt-Jakob disease.