This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Ersdal, C. Articles by Landsverk, T. Search for Related Content PubMed PubMed Citation Articles by Ersdal, C. Articles by Landsverk, T.

Mapping PrP^Sc Propagation in Experimental and Natural Scrapie in Sheep with Different PrP Genotypes

Departments of Production Animal Clinical Sciences (CE, MJU) and Basic Sciences and Aquatic Medicine (CE, AE, TL), Norwegian School of Veterinary Science, Oslo, Norway; Department of Pathology, National Veterinary Institute, Oslo, Norway (SLB); and INRA, Tours-Nouzilly, France (PS)

Twenty-one orally inoculated and seven naturally infected sheep with scrapie were examined for PrP^Sc in peripheral tissues and in the central nervous system (CNS), using immunohistochemistry. In the inoculated group, VRQ (valine at codon 136, arginine at codon 154 and glutamine at codon 171)/VRQ sheep generally had a greater accumulation of the pathologic form of prion protein (PrP^Sc) in peripheral tissues, as compared with VRQ/ARQ (alanine at codon 136, arginine at codon 154, and glutamine at codon 171) animals at corresponding time points after inoculation. PrP^Sc was not detected in the ileal Peyer's patch, the spleen, the superficial cervical lymph node, and peripheral nervous tissues of several inoculated VRQ/ARQ animals. All inoculated VRQ/VRQ sheep, but only one of eight inoculated VRQ/ARQ animals, were PrP^Sc-positive in the CNS. Thus, the propagation of PrP^Sc seemed slower and more limited in VRQ/ARQ animals. Tissue and cellular localization of PrP^Sc suggested that PrP^Sc was disseminated through three different routes. PrP^Sc-positive cells in lymph node sinuses and in lymphatics indicated spreading by lymph. The sequential appearance of PrP^Sc in the peripheral nervous system and the CNS, with satellite cells as early targets, suggested the periaxonal transportation of PrP^Sc through supportive cells. Focal areas of vascular amyloid-like PrP^Sc in the brain of five sheep, suggested the hematogenous dissemination of PrP^Sc. There was a poor correlation between the amount of PrP^Sc in the CNS and clinical signs. One subclinically affected sheep showed widespread PrP^Sc accumulation in the CNS, whereas three sheep had early clinical signs without detectable PrP^Sc in the CNS. A VV₁₃₆ (homozygous for valine at codon 136) sheep inoculated with ARQ/ARR (alanine at codon 136, arginine at codon 154, and arginine at codon 171) tissue succumbed to disease, demonstrating successful heterologous transmission. Less susceptible sheep receiving VRQ/VRQ or ARQ/ARR material were PrP^Sc-negative by immunohistochemistry, enzyme-linked immunosorbent assay, and western blot.

Key words: Central; peripheral nervous tissues; ELISA; immunohistochemistry; lymphoid tissues; placenta; PrP^Sc; sheep scrapie; western blot.

Request reprints from Dr. Cecilie Ersdal, Norwegian School of Veterinary Science, PO Box 8146 Dep, 0033 Oslo (Norway). E-mail: cecilie.ersdal{at}veths.no

This article has been cited by other articles:

				J. T. McKay, T. A. Brigner, B. E. Caplin, K. S. McCurdy, and R. L. Forde A real-time polymerase chain reaction assay to detect single nucleotide polymorphisms at codon 171 in the prion gene for the genotyping of scrapie susceptibility in sheep J Vet Diagn Invest, March 1, 2008; 20(2): 209 - 212. [Abstract] [Full Text] [PDF]

				L. Austbo, A. Espenes, I. Olsaker, C. McL. Press, and G. Skretting Increased PrP mRNA expression in lymphoid follicles of the ileal Peyer's patch of sheep experimentally exposed to the scrapie agent J. Gen. Virol., July 1, 2007; 88(7): 2083 - 2090. [Abstract] [Full Text] [PDF]

				T. Seuberlich, C. Botteron, S. L. Benestad, H. Brunisholz, R. Wyss, U. Kihm, H. Schwermer, M. Friess, A. Nicolier, D. Heim, et al. Atypical scrapie in a swiss goat and implications for transmissible spongiform encephalopathy surveillance J Vet Diagn Invest, January 1, 2007; 19(1): 2 - 8. [Abstract] [Full Text] [PDF]

				J. J. Greenlee, A. N. Hamir, and M. H. West Greenlee Abnormal prion accumulation associated with retinal pathology in experimentally inoculated scrapie-affected sheep. Vet. Pathol., September 1, 2006; 43(5): 733 - 739. [Abstract] [Full Text] [PDF]

				J. W Ironside, M. T Bishop, K. Connolly, D. Hegazy, S. Lowrie, M. Le Grice, D. L Ritchie, L. M McCardle, and D. A Hilton Variant Creutzfeldt-Jakob disease: prion protein genotype analysis of positive appendix tissue samples from a retrospective prevalence study BMJ, May 20, 2006; 332(7551): 1186 - 1188. [Abstract] [Full Text] [PDF]