title: Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD.
abstract: 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.
authors.affiliation: Institut Scientifique de Recherche Agronomique (INRA), UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, France. vincent.beringue@jouy.inra.fr
authors.forename: Vincent
authors.initials: V
authors.lastname: Béringue
authors.forename: Annick
authors.initials: A
authors.lastname: Le Dur
authors.forename: Philippe
authors.initials: P
authors.lastname: Tixador
authors.forename: Fabienne
authors.initials: F
authors.lastname: Reine
authors.forename: Laurence
authors.initials: L
authors.lastname: Lepourry
authors.forename: Armand
authors.initials: A
authors.lastname: Perret-Liaudet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Haïk
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Vilotte
authors.forename: Michel
authors.initials: M
authors.lastname: Fontés
authors.forename: Hubert
authors.initials: H
authors.lastname: Laude
mesh_terms: D000818:Animals; D007562:Creutzfeldt-Jakob Syndrome / Q000473:pathology* / Q000635:transmission; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000473:pathology* / Q000635:transmission