Prion infectivity in variant Creutzfeldt-Jakob disease rectum.
BACKGROUND
Disease-related prion protein (PrP(Sc)) is readily detectable in lymphoreticular tissues in variant Creutzfeldt-Jakob disease (vCJD), but not in other forms of human prion disease. This distinctive pathogenesis, with the unknown population prevalence of asymptomatic vCJD infection, has led to significant concerns that secondary transmission of vCJD prions will occur through a wide range of surgical procedures. To date PrP(Sc):prion infectivity ratios have not been determined in vCJD, and it is unknown whether vCJD prions are similar to experimental rodent prions, where PrP(Sc) concentration typically reflects infectious prion titre.


OBJECTIVE
To investigate prion infectivity in vCJD tissue containing barely detectable levels of PrP(Sc).


METHODS
Transgenic mice expressing only human PrP (Tg(HuPrP129M(+/+)Prnp(o/o))-35 and Tg(HuPrP129M(+/+)Prnp(o/o))-45 mice) were inoculated with brain or rectal tissue from a previously characterised patient with vCJD. These tissues contain the maximum and minimum levels of detectable PrP(Sc) that have been observed in vCJD.


RESULTS
Efficient transmission of prion infection was observed in transgenic mice inoculated with vCJD rectal tissue containing PrP(Sc) at a concentration of 10(4.7)-fold lower than that in vCJD brain.


CONCLUSIONS
These data confirm the potential risks for secondary transmission of vCJD prions via gastrointestinal procedures and support the use of PrP(Sc) as a quantitative marker of prion infectivity in vCJD tissues.
Wadsworth
J D F
JD
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.
Joiner
S
S
Fox
K
K
Linehan
J M
JM
Desbruslais
M
M
Brandner
S
S
Asante
E A
EA
Collinge
J
J
D000818:Animals; D001921:Brain / Q000378:metabolism; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism / Q000635:transmission*; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D018621:PrPC Proteins / Q000032:analysis; D018620:PrPSc Proteins / Q000032:analysis; D011328:Prions / Q000032:analysis*; D012007:Rectum / Q000378:metabolism
D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions