Scrapie Infectivity and Proteinase K‐Resistant Prion Protein in Sheep Placenta, Brain, Spleen, and Lymph Node: Implications for Transmission and Antemortem Diagnosis

Race, Richard E.; Jenny, Allen L.; Sutton, Diane L.

doi:10.1086/515669

Cited by 176 publications

(143 citation statements)

References 20 publications

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“…This may be because they are more likely to propagate scrapie within their £ock once a ¢rst case has been acquired. This is certainly consistent with long-standing hypotheses about the role of infected reproductive tissues in the spread of scrapie (Pattison et al 1972;Pattison & Millson 1961;Race et al 1998;Ikegami et al 1991;Hourrigan & Klingsporn 1996). However an alternative explanation is simply that farms that breed a large proportion of their £ock are more likely to keep infected animals for long enough to see clinical disease.…”

Section: Discussionsupporting

confidence: 83%

Scrapie transmission in Britain: a recipe for a mathematical model

McLean

Hoek

Hoinville

et al. 1999

Proc. R. Soc. Lond. B

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Responses to an anonymous postal survey concerning scrapie are analysed. Risk factors associated with farms that have had scrapie are identi¢ed as size, geographical region, lambing practices and holding of certain breeds. Further analysis of farms that have scrapie only in bought-in animals reveals that such farms tend to breed a smaller proportion of their replacement animals than farms without scrapie. Farms that have had scrapie in home-bred animals have attributes associated with breeding many animals: large numbers of rams bought, few ewes bought, and many animals that are home-bred. The demography of British sheep farms as described by size, breeds, purchasing behaviour, age structure and proportion of animals that are home-bred is summarized. British farms with scrapie reveal certain special features: they have more sheep that are found dead, more elderly ewes and more cases of scab.

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Section: Discussionsupporting

confidence: 83%

Scrapie transmission in Britain: a recipe for a mathematical model

McLean

Hoek

Hoinville

et al. 1999

Proc. R. Soc. Lond. B

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“…This observation is consistent with the well-recognized infectivity of fetal membranes. 32 Similar to Andreoletti et al, 2 PrP sc was found to be restricted to fetal tissues. Because placentomes were not analyzed specifically for macrophages, the possibility of PrP sc deposits occurring in macrophages of the (maternal) caruncle or at the interface between fetal and maternal tissues remains.…”

Section: Discussionsupporting

confidence: 65%

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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“…However, it has largely been concluded that autolysis does not compromise the accuracy of assays that detect the proteinase-resistant, pathogenic isoform of the prion protein (PrP res ). 2,5,7,8,12,16 It was hypothesized that over a relatively long period of time, exposure to heat may have a more substantial effect on PrP res immunodection than previously considered. The objective of the present study was to characterize PrP CWD detectability with time in brain samples subjected to heat in vitro as determined by Western blot.…”

mentioning

confidence: 99%

Effect of Time and Temperature on PrP^CWD Immunoreactivity as Evidenced by Western Blot

et al. 2007

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Abstract. The protease-resistant infectious prion protein, PrP res , that causes transmissible spongiform encephalopathies, is remarkably resistant to conventional physical and chemical sterilization methods, including heat. It was hypothesized that thermal-dependent PrP res degradation has been underestimated, and the effect of prolonged incubation at 37uC, 55uC, and 80uC on PrP res detection was examined using brain homogenates from chronic wasting disease-affected elk and mule deer (PrP CWD ). Immunoblotting demonstrated progressive loss of PrP CWD immunoreactivity with time in all incubated samples as temperature increased, and PrP CWD was virtually undetectable after 90 days of incubation at 55uC and 80uC. These results indicate that decontamination methods and tissue disposal systems maintaining elevated temperatures for long periods of time could interfere with immunodetection, and the reliability of assays for PrP res detection could be compromised when applied to tissues exposed to heat with time. Although these results may suggest that such prolonged heat treatment could destroy prions, the observed loss of immunoreactivity does not necessarily correlate with a concurrent loss of infectivity. Bioassay is needed to determine if samples that have been incubated under these conditions retain infectivity.

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Scrapie Infectivity and Proteinase K‐Resistant Prion Protein in Sheep Placenta, Brain, Spleen, and Lymph Node: Implications for Transmission and Antemortem Diagnosis

Cited by 176 publications

References 20 publications

Scrapie transmission in Britain: a recipe for a mathematical model

Scrapie transmission in Britain: a recipe for a mathematical model

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

Effect of Time and Temperature on PrP^CWD Immunoreactivity as Evidenced by Western Blot

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Scrapie Infectivity and Proteinase K‐Resistant Prion Protein in Sheep Placenta, Brain, Spleen, and Lymph Node: Implications for Transmission and Antemortem Diagnosis

Cited by 176 publications

References 20 publications

Scrapie transmission in Britain: a recipe for a mathematical model

Scrapie transmission in Britain: a recipe for a mathematical model

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

Effect of Time and Temperature on PrPCWD Immunoreactivity as Evidenced by Western Blot

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

Effect of Time and Temperature on PrP^CWD Immunoreactivity as Evidenced by Western Blot