Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD.
BACKGROUND
The evolution of the variant Creutzfeldt-Jakob disease (vCJD) epidemic is hazardous to predict due to uncertainty in ascertaining the prevalence of infection and because the disease might remain asymptomatic or produce an alternate, sporadic-like phenotype.


RESULTS
Transgenic mice were produced that overexpress human prion protein with methionine at codon 129, the only allele found so far in vCJD-affected patients. These mice were infected with prions derived from variant and sporadic CJD (sCJD) cases by intracerebral or intraperitoneal route, and transmission efficiency and strain phenotype were analyzed in brain and spleen. We showed that i) the main features of vCJD infection in humans, including a prominent involvement of the lymphoid tissues compared to that in sCJD infection were faithfully reproduced in such mice; ii) transmission of vCJD agent by intracerebral route could lead to the propagation of either vCJD or sCJD-like prion in the brain, whereas vCJD prion was invariably propagated in the spleen, iii) after peripheral exposure, inefficient neuroinvasion was observed, resulting in an asymptomatic infection with life-long persistence of vCJD prion in the spleen at stable and elevated levels.


CONCLUSIONS
Our findings emphasize the possibility that human-to-human transmission of vCJD might produce alternative neuropathological phenotypes and that lymphoid tissue examination of CJD cases classified as sporadic might reveal an infection by vCJD-type prions. They also provide evidence for the strong propensity of this agent to establish long-lasting, subclinical vCJD infection of lymphoreticular tissues, thus amplifying the risk for iatrogenic transmission.
Béringue
Vincent
V
Institut Scientifique de Recherche Agronomique (INRA), UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, France. vincent.beringue@jouy.inra.fr
Le Dur
Annick
A
Tixador
Philippe
P
Reine
Fabienne
F
Lepourry
Laurence
L
Perret-Liaudet
Armand
A
Haïk
Stéphane
S
Vilotte
Jean-Luc
JL
Fontés
Michel
M
Laude
Hubert
H
D000818:Animals; D007562:Creutzfeldt-Jakob Syndrome / Q000473:pathology* / Q000635:transmission; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000473:pathology* / Q000635:transmission