Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates a new prion strain.
The genotype (methionine or valine) at polymorphic codon 129 of the human prion protein (PrP) gene and the type (type 1 or type 2) of abnormal isoform of PrP (PrP(Sc)) are major determinants of the clinicopathological phenotypes of sporadic Creutzfeldt-Jakob disease (sCJD). Here we found that the transmission of sCJD prions from a patient with valine homozygosity (129V/V) and type 2 PrP(Sc) (sCJD-VV2 prions) to mice expressing human PrP with methionine homozygosity (129M/M) generated unusual PrP(Sc) intermediate in size between type 1 and type 2. The intermediate type PrP(Sc) was seen in all examined dura mater graft-associated CJD cases with 129M/M and plaque-type PrP deposits (p-dCJD). p-dCJD prions and sCJD-VV2 prions exhibited similar transmissibility and neuropathology, and the identical type of PrP(Sc) when inoculated into PrP-humanized mice with 129M/M or 129V/V. These findings suggest that p-dCJD could be caused by cross-sequence transmission of sCJD-VV2 prions.
Kobayashi
Atsushi
A
Division of CJD Science and Technology, Department of Prion Research, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Asano
Masahiro
M
Mohri
Shirou
S
Kitamoto
Tetsuyuki
T
D000818:Animals; D001344:Autopsy; D001921:Brain / Q000378:metabolism; D003062:Codon; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis* / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D020033:Protein Isoforms; D014633:Valine / Q000737:chemistry
D003062:Codon; D011328:Prions; D020033:Protein Isoforms; D014633:Valine