title: Classical scrapie prions are associated with peripheral blood monocytes and T-lymphocytes from naturally infected sheep.
abstract: BACKGROUND
  Classical scrapie is a transmissible spongiform encephalopathy (TSE) that affects sheep and goats. Our previous bioassay studies in lambs revealed that scrapie prions could be detected in association with peripheral blood monocular cells (PBMC), B lymphocytes and platelet-rich plasma fractions. In the present study, bioassay in lambs was again used to determine if scrapie prions are associated with the other two subsets of PBMC, monocytes and T lymphocytes.
  
  
  RESULTS
  PBMC, monocytes and T lymphocytes were isolated from two preclinically affected VRQ/VRQ sheep naturally infected with classical ovine scrapie and intravenously transfused into VRQ/VRQ lambs post-weaning. As determined using standard immunohistochemistry for scrapie, abnormal isoforms of prion protein were detected in lymphoid tissues of lambs inoculated with PBMC (4/4 recipient lambs), monocytes (2/5) and T lymphocytes (1/4). Prion protein misfolding activity was detected by serial protein misfolding cyclic amplification (sPMCA) in PBMC from monocyte and T lymphocyte recipient sheep in agreement with antemortem rectal biopsy results, but such prion protein misfolding activity was not detected from other recipients.
  
  
  CONCLUSIONS
  These findings show that scrapie prions are associated with monocytes and T lymphocytes circulating in the peripheral blood of sheep naturally infected with classical scrapie. Combined with our previous findings, we can now conclude that all three major subsets of PBMC can harbor prions during preclinical disease and thus, present logical targets for development of a sensitive assay to detect scrapie prions. In this regard, we have also demonstrated that sPMCA can be used to detect scrapie prions associated with PBMC.
authors: Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164-6630, USA. rohana1@vetmed.wsu.edu.
authors: Rohana P
authors: RP
authors: Dassanayake
authors: Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164-6630, USA. smadsen@vetmed.wsu.edu.
authors: Sally A
authors: SA
authors: Madsen-Bouterse
authors: Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Pullman, WA, 99164-6630, USA. ttruscot@vetmed.wsu.edu.
authors: Thomas C
authors: TC
authors: Truscott
authors: Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Pullman, WA, 99164-6630, USA. dongyue@vetmed.wsu.edu.
authors: Dongyue
authors: D
authors: Zhuang
authors: Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Pullman, WA, 99164-6630, USA. michelle.mousel@ars.usda.gov.
authors: Michelle R
authors: MR
authors: Mousel
authors: Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164-6630, USA. davisw@vetmed.wsu.edu.
authors: William C
authors: WC
authors: Davis
authors: Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164-6630, USA. david.schneider1@ars.usda.gov.|Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Pullman, WA, 99164-6630, USA. david.schneider1@ars.usda.gov.
authors: David A
authors: DA
authors: Schneider
mesh_terms: D000818:Animals; D009000:Monocytes / Q000378:metabolism*; D011328:Prions / Q000032:analysis*; D012608:Scrapie / Q000097:blood*; D012756:Sheep; D012757:Sheep Diseases / Q000097:blood*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D011328:Prions