title: Foodborne-Transmitted Prions From the Brain of Cows With Bovine Spongiform Encephalopathy Ascend in Afferent Neurons to the Simian Central Nervous System and Spread to Tonsils and Spleen at a Late Stage of the Incubation Period.
abstract: BACKGROUND
  Protease-resistant prion protein (PrP(res)) accumulation in lymphoreticular tissues indicates prion infection. To date, tonsillectomy and appendectomy samples have been used in population prevalence surveys to detect clinically silent carriers of variant Creutzfeldt-Jakob disease (vCJD). However, the temporal sequence of prion spread in the human body is still not known. We therefore traced the temporal-spatial pattern of PrP(res) accumulation in the body of a simian vCJD model.
  
  
  METHODS
  Cynomolgus monkeys were fed brain of (eleven) cows with bovine spongiform encephalopathy, and some were euthanized before and some after onset of neurological signs. PrP(res) was detected in tissues by a paraffin-embedded tissue blot technique and a semiquantitative Western immunoblot assay.
  
  
  RESULTS
  Bovine spongiform encephalopathy (BSE)-associated prions were preferentially transported from the gut to the central nervous system (CNS) along sensory nerve fibers and initially entered the simian CNS at lumbar spinal cord levels. In asymptomatic animals, we found BSE in 50% and 12% of gut- and tonsil-derived samples, respectively.
  
  
  CONCLUSIONS
  Unlike in rodents and ruminants, foodborne BSE-associated prions entered the simian CNS via afferent neurons. From sites of initial CNS invasion, prions spread centrifugally to tonsils and spleen at an advanced stage of the incubation period, thus explaining why tonsil specimens were not reliable for detection of simian disease carriers before onset of clinical signs.
authors.affiliation: Paul Ehrlich Institut, Federal Institute for Vaccines and Biomedicines, Langen.
authors.forename: Edgar
authors.initials: E
authors.lastname: Holznagel
authors.affiliation: Paul Ehrlich Institut, Federal Institute for Vaccines and Biomedicines, Langen.
authors.forename: Barbara
authors.initials: B
authors.lastname: Yutzy
authors.affiliation: Paul Ehrlich Institut, Federal Institute for Vaccines and Biomedicines, Langen.
authors.forename: Carina
authors.initials: C
authors.lastname: Kruip
authors.affiliation: Swedish Institute for Infectious Disease Control, Solna.
authors.forename: Par
authors.initials: P
authors.lastname: Bierke
authors.affiliation: Department of Neuropathology, University Hospital, Georg August University, Göttingen, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Schulz-Schaeffer
authors.affiliation: Paul Ehrlich Institut, Federal Institute for Vaccines and Biomedicines, Langen.
authors.forename: Johannes
authors.initials: J
authors.lastname: Löwer
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D002417:Cattle; D002490:Central Nervous System / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000453:epidemiology* / Q000662:veterinary; D004195:Disease Models, Animal; D016643:Encephalopathy, Bovine Spongiform / Q000635:transmission*; D005517:Foodborne Diseases / Q000473:pathology* / Q000662:veterinary; D008252:Macaca fascicularis; D008461:Meat Products; D009475:Neurons, Afferent / Q000473:pathology; D014066:Palatine Tonsil / Q000473:pathology; D018620:PrPSc Proteins / Q000378:metabolism*; D015995:Prevalence; D013048:Specimen Handling; D013154:Spleen / Q000473:pathology
chemical_list: D018620:PrPSc Proteins
keywords: BSE; Creutzfeldt-Jakob disease; appendectomy; macaque; preclinical; prevalence; prion; tonsillectomy; vCJD