vCJD prion acquires altered virulence through trans-species infection.
Variant Creutzfeldt-Jakob disease (vCJD) appears to be caused by infection with the bovine spongiform encephalopathy (BSE) agent. To date, all patients with vCJD are homozygous for methionine at codon 129 of the PrP gene. To investigate the relationship between polymorphism at codon 129 and susceptibility to BSE or vCJD prions, we performed splenic follicular dendritic cell assay with humanized knock-in mice through peripheral infection. All humanized knock-in mice showed little or no susceptibility to BSE prions. Only the subset of humanized knock-in mice with codon 129 Met/Met genotype showed weak susceptibility by Western blotting. Surprisingly, we succeeded in the transmission of vCJD prions to humanized knock-in mice not only with codon 129 Met/Met but also with codon 129 Met/Val. Humanized knock-in mice with codon 129 Val/Val were not susceptible. The results suggest that human heterozygotes at codon 129 are also at risk for secondary infection with vCJD.
Division 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.
Masahiro
M
Asano
Shirou
S
Mohri
James W
JW
Ironside
Mamoru
M
Ito
Norikazu
N
Tamaoki
Tetsuyuki
T
Kitamoto
D000818:Animals; D002417:Cattle; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004198:Disease Susceptibility; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011328:Prions / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D013045:Species Specificity; D013154:Spleen / Q000378:metabolism; D014774:Virulence; D015047:Zoonoses
D011328:Prions