title: Atypical BSE (BASE) transmitted from asymptomatic aging cattle to a primate.
abstract: BACKGROUND
  Human variant Creutzfeldt-Jakob Disease (vCJD) results from foodborne transmission of prions from slaughtered cattle with classical Bovine Spongiform Encephalopathy (cBSE). Atypical forms of BSE, which remain mostly asymptomatic in aging cattle, were recently identified at slaughterhouses throughout Europe and North America, raising a question about human susceptibility to these new prion strains.
  
  
  RESULTS
  Brain homogenates from cattle with classical BSE and atypical (BASE) infections were inoculated intracerebrally into cynomolgus monkeys (Macacca fascicularis), a non-human primate model previously demonstrated to be susceptible to the original strain of cBSE. The resulting diseases were compared in terms of clinical signs, histology and biochemistry of the abnormal prion protein (PrPres). The single monkey infected with BASE had a shorter survival, and a different clinical evolution, histopathology, and prion protein (PrPres) pattern than was observed for either classical BSE or vCJD-inoculated animals. Also, the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine.
  
  
  CONCLUSIONS
  Our results point to a possibly higher degree of pathogenicity of BASE than classical BSE in primates and also raise a question about a possible link to one uncommon subset of cases of apparently sporadic CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of atypical strains should temper the urge to relax measures currently in place to protect public health from accidental contamination by BSE-contaminated products.
authors: Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France. emmanuel.comoy@cea.fr
authors: Emmanuel E
authors: EE
authors: Comoy
authors: Cristina
authors: C
authors: Casalone
authors: Nathalie
authors: N
authors: Lescoutra-Etchegaray
authors: Gianluigi
authors: G
authors: Zanusso
authors: Sophie
authors: S
authors: Freire
authors: Dominique
authors: D
authors: Marcé
authors: Frédéric
authors: F
authors: Auvré
authors: Marie-Magdeleine
authors: MM
authors: Ruchoux
authors: Sergio
authors: S
authors: Ferrari
authors: Salvatore
authors: S
authors: Monaco
authors: Nicole
authors: N
authors: Salès
authors: Maria
authors: M
authors: Caramelli
authors: Philippe
authors: P
authors: Leboulch
authors: Paul
authors: P
authors: Brown
authors: Corinne I
authors: CI
authors: Lasmézas
authors: Jean-Philippe
authors: JP
authors: Deslys
mesh_terms: D000375:Aging; D000818:Animals; D002417:Cattle / Q000235:genetics* / Q000254:growth & development; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000635:transmission; D016643:Encephalopathy, Bovine Spongiform / Q000235:genetics / Q000635:transmission; D005625:Frontal Lobe / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D008252:Macaca fascicularis / Q000235:genetics*; D013045:Species Specificity; D014774:Virulence