Predicting susceptibility and incubation time of human-to-human transmission of vCJD.
BACKGROUND
Identification of possible transmission of variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion has caused concern over spread of the disease within the human population. We aimed to model iatrogenic spread to enable a comparison of transmission efficiencies of vCJD and bovine spongiform encephalopathy (BSE) and an assessment of the effect of the codon-129 polymorphism on human susceptibility.


METHODS
Mice were produced to express human or bovine prion protein (PrP) by direct replacement of the mouse PrP gene. Since the human PrP gene has variation at codon 129, with MM, VV, and MV genotypes, three inbred lines with an identical genetic background were produced to express human PrP with the codon-129 MM, MV, and VV genotypes. Mice were inoculated with BSE or vCJD and assessed for clinical and pathological signs of disease.


RESULTS
BSE was transmitted to the bovine line but did not transmit to the human lines. By contrast, vCJD was transmitted to all three human lines with different pathological characteristics for each genotype and a gradation of transmission efficiency from MM to MV to VV.


CONCLUSIONS
Transmission of BSE to human beings is probably restricted by the presence of a significant species barrier. However, there seems to be a substantially reduced barrier for human-to-human transmission of vCJD. Moreover, all individuals, irrespective of codon-129 genotype, could be susceptible to secondary transmission of vCJD through routes such as blood transfusion. A lengthy preclinical disease is predicted by these models, which may represent a risk for further disease transmission and thus a significant public-health issue.
Bishop
M T
MT
National CJD Surveillance Unit, Bryan Matthews Building, Western General Hospital, Edinburgh, UK.
Hart
P
P
Aitchison
L
L
Baybutt
H N
HN
Plinston
C
C
Thomson
V
V
Tuzi
N L
NL
Head
M W
MW
Ironside
J W
JW
Will
R G
RG
Manson
J C
JC
D000682:Amyloid / Q000235:genetics*; D000818:Animals; D001803:Blood Transfusion; D002417:Cattle; D003062:Codon; D007562:Creutzfeldt-Jakob Syndrome / Q000635:transmission*; D016643:Encephalopathy, Bovine Spongiform / Q000635:transmission*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007049:Iatrogenic Disease; D051379:Mice; D008822:Mice, Transgenic; D011110:Polymorphism, Genetic; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000235:genetics*; D012307:Risk Factors; D015047:Zoonoses
D000682:Amyloid; D003062:Codon; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D011498:Protein Precursors