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Predicting
susceptibility and incubation time of
human-to-human transmission of vCJD.
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Bishop MT,
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Hart P,
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Aitchison L,
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Baybutt HN,
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Plinston C,
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Thomson V,
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Tuzi NL,
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Head MW,
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Ironside JW,
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Will RG,
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Manson JC.
National CJD
Surveillance Unit, Bryan Matthews Building,
Western General Hospital, Edinburgh, UK.
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. FINDINGS: 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. INTERPRETATION:
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.
PMID: 16632309 [PubMed - indexed for MEDLINE]