Detection of PrPSc in Lymphoid Tissues of Lambs Experimentally Exposed to the Scrapie Agent

Heggebø, Ragna; Press, Charles McL.; Gunnes, Gjermund; Ulvund, Martha J.; Tranulis, Michael A.; Lsverk, T

doi:10.1053/jcpa.2002.0625

Cited by 57 publications

(41 citation statements)

References 25 publications

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“…20 Furthermore, the proximity of nerve endings and PrP sc in lymphoid follicles has been demonstrated. 14,31 Conversely, in this study the authors failed to observe a pattern of PrP sc accumulation in lymphoid tissues that would suggest travel of PrP sc through the lymphatic vessels or blood stream. For instance, PrP sc was not detected in the glandular tissue of the mammary gland, the tributary region of the mammary lymph nodes; yet, the mammary lymph node regularly accumulated PrP sc .…”

Section: Discussioncontrasting

confidence: 66%

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Caplazi

O’Rourke²,

Wolf

et al. 2004

J VET Diagn Invest

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Abstract. Sheep scrapie is a prion disease that requires interaction of exogenous prions with host prion protein (PrP) supporting prion formation. Disease is associated with deposition of a host-generated conformational variant of PrP, PrP sc , in a variety of tissues, including brain, resulting in fatal spongiform encephalopathy. Efficiency of PrP sc formation is determined by polymorphisms in the PrP-coding sequence. This article adds to previous data of natural sheep scrapie, concentrating on the effect of host genotype and age on PrP sc accumulation patterns during preclinical and clinical disease. Two entire scrapie-infected, predominantly Suffolk-cross, sheep flocks euthanized for regulatory purposes were genotyped and analyzed for PrP sc deposition in various tissues using single-and dual-label immunohistochemistry. Scrapie, as defined by PrP sc deposition, occurred in 13/80 sheep. Preclinical disease was evident in nearly 70% of infected sheep, ranging in age from 14 months to 7 years. PrP sc accumulated systemically in the nervous tissue, various lymphoid tissues, both alimentary tract related and non-alimentary tract related, and the placenta. Clinical neurological illness was always associated with spongiform encephalopathy and PrP sc deposition in the brain. Only 6 of 9 sheep with preclinical scrapie had PrP sc deposition in the brain but widespread PrP sc deposition in peripheral lymphoid tissue, supporting previous data showing peripheral PrP sc accumulation preceding deposition in the brain. PrP sc colocalized with a marker for follicular dendritic cells throughout the lymphoid system. PrP sc also accumulated in the peripheral nervous system, particularly the nervous supply of the gastrointestinal tract. Abundant PrP sc was evident in trophoblast cells of placentomes but not in the endometrium, myometrium, or associated nervous plexus. PrP sc deposits were not observed in the mammary parenchyma or bone marrow. Scrapie susceptibility was defined genetically by PrP codon 171: PrP sc deposition was restricted to PrP genotype AA 136 RR 154 QQ 171 in 12/13 cases or AV 136 RR 154 QQ 171 in 1/13 cases. The earliest accumulation was observed in the single VRQ/ARQ heterozygous animal, consistent with the reported high scrapie susceptibility and brief incubation period observed in breeds with predominance of the V 136 R 154 Q 171 allele. Disease occurred within, as well as independent of, motherdaughter lines, suggesting both maternal and nonmaternal transmission in the flocks.

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Section: Discussioncontrasting

confidence: 66%

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Caplazi

O’Rourke²,

Wolf

et al. 2004

J VET Diagn Invest

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“…Indeed, the early presence of PrP Sc in the RPLN and the DJLN, in addition to the tonsil and the IPP, was demonstrated in lambs as early as 5 weeks after infection, using the same experimental procedure as described in this study. 25 Lower accumulation of PrP Sc in the spleen and the SCLN as compared with the RPLN and the DJLN could be because of the close association with the MALT and the probable transport of PrP Sc through lymph to the latter tissues. Dissemination of PrP Sc by blood to the spleen and lymph nodes not associated with the digestive tract was suggested in a sequential study of scrapie in mice.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2005

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Abstract. 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 VV 136 (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.

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“…Similar findings have been described in studies of the pathogenesis in sheep and mule deer. 1,4,[8][9][10][11]18,19 Prospective studies on captive and free-ranging elk using this technique are in progress. These studies will delineate the diagnostic sensitivity and specificity of RAMALT screening as a method for identification of infected elk herds as part of an integrated management program to reduce the incidence of CWD in Rocky Mountain elk.…”

Section: 4mentioning

confidence: 99%

Antemortem Detection of PrP^CWD in Preclinical, Ranch-Raised Rocky Mountain Elk (Cevvus Elaphus Nelsoni) by Biopsy of the Rectal Mucosa

et al. 2009

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Abstract. Antemortem biopsy of the rectal mucosa was evaluated as a method for the preclinical diagnosis of chronic wasting disease (CWD) in a herd of ranch-raised Rocky Mountain elk (Cervus elaphus nelsoni) quarantined because of exposure to CWD. Biopsy samples were obtained from 41 elk during the winter of [2005][2006] and from 26 elk from that herd still alive and available for testing during the winter of 2006-2007. Samples were examined for PrP CWD , the protein marker for CWD infection, by immunohistochemistry. PrP CWD was detected in follicles of the rectoanal mucosa-associated lymphoid tissue in biopsy samples from 1 elk with clinical signs of chronic wasting disease and 5 clinically normal elk. The diagnosis was confirmed in all 6 animals by postmortem analysis of brain and peripheral lymph nodes. PrP CWD was also observed in the submucosal plexus and myenteric plexus of the enteric nervous system, and in close association with nonmyelinated mucosal and submucosal nerve fibers. In antemortem rectal biopsy samples from positive animals, immunostaining was consistently observed in approximately 60% of the mucosa-associated lymphoid tissue follicles if 10 or more total follicles per biopsy were present for evaluation. Most antemortem biopsy samples obtained from elk younger than 6.5 years contained at least 10 follicles per rectal mucosal biopsy. These findings support the analysis of antemortem biopsy of the rectal mucosa samples as part of an integrated strategy to manage chronic wasting disease in Rocky Mountain elk.

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Detection of PrPSc in Lymphoid Tissues of Lambs Experimentally Exposed to the Scrapie Agent

Cited by 57 publications

References 25 publications

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

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

Antemortem Detection of PrP^CWD in Preclinical, Ranch-Raised Rocky Mountain Elk (Cevvus Elaphus Nelsoni) by Biopsy of the Rectal Mucosa

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Detection of PrPSc in Lymphoid Tissues of Lambs Experimentally Exposed to the Scrapie Agent

Cited by 57 publications

References 25 publications

Biology of PrPsc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Biology of PrPsc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Mapping PrPScPropagation in Experimental and Natural Scrapie in Sheep with Different PrP Genotypes

Antemortem Detection of PrPCWD in Preclinical, Ranch-Raised Rocky Mountain Elk (Cevvus Elaphus Nelsoni) by Biopsy of the Rectal Mucosa

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Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

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

Antemortem Detection of PrP^CWD in Preclinical, Ranch-Raised Rocky Mountain Elk (Cevvus Elaphus Nelsoni) by Biopsy of the Rectal Mucosa