Oral Inoculation of Sheep with the Agent of Bovine Spongiform Encephalopathy (BSE). 1. Onset and Distribution of Disease-specific PrP Accumulation in Brain and Viscera

Jeffrey, Martin; Ryder, Stephen; Martin, Stuart; Hawkins, S. A. C.; Terry, Linda A.; Berthelin-Baker, C.; Bellworthy, S. J.

doi:10.1053/jcpa.2001.0465

Cited by 160 publications

(173 citation statements)

References 24 publications

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“…This observation contrasts somewhat to a similar study that reports early accumulation of PrP sc in tingible body macrophages of the germinal center. 17 Failure to observe PrP sc in tingible body macrophages may be because of examination of tissues at a later stage of disease because PrP sc derives from scavenging exogenous PrP sc rather than synthesis within that cell type. 15 The distribution of PrP sc observed in this study underscores the importance of the germinal center and FDC for the peripheral amplification of PrP sc and is consistent with neurogenic spread from sites of primary amplification to the CNS.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…Based on published data ( Jeffrey et al 2001;van Keulen et al 2002;Bellworthy et al 2005b), we make conservative estimates of test sensitivity (see table 7 of electronic supplementary material) that are reflected in poor performance from these strategies, reducing the infectious load entering the food chain from four flocks by around 60%.…”

Section: (I) Prpmentioning

confidence: 99%

“…Speculation has been driven by experimental results showing that sheep are susceptible to BSE infection from intravenous, intracerebral (ic) and oral challenge ( Foster et al 2001a,b;Jeffrey et al 2001;Houston et al 2003). Furthermore, a natural case of BSE infection in a French goat has recently been confirmed ( Froissart 2004), and preliminary results suggest that a second infected goat has been located in Scotland (DEFRA 2005).…”

Section: Introductionmentioning

confidence: 99%

“…While infectivity in cattle is largely confined to the nervous system ( Wells et al 1998), the same is not true for sheep. BSE infectivity and disease-associated prion protein have been found to be widespread throughout the body of an infected sheep ( Foster et al 2001b;Jeffrey et al 2001;Ferguson et al 2002;Bellworthy et al 2005b;Gonzalez et al 2005), even in the early stages of infection. Furthermore, a number of tissues that have been shown to carry infectivity are currently eaten by humans and cannot be completely removed from a sheep carcass.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Quantifying the risk from ovine BSE and the impact of control strategies

Fryer

Baylis

Sivam³

et al. 2007

Proc. R. Soc. B.

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Although no naturally infected sheep with bovine spongiform encephalopathy (BSE) has ever been discovered, it remains possible that BSE once infected the UK sheep population, has been transmitted between sheep, and is still present today. We constructed a mathematical model to assess the current maximum theoretical exposure to consumers from BSE-infected ovine material and to estimate the risk reduction that could be achieved by abattoir-based control options if BSE-infected sheep were ever found in the national flock. We predict that, if present, the exposure to consumers from a single BSE-infected sheep would be high: one sheep, close to the end of its incubation period, is likely to contribute 10-1000 times more infectious material than a fully infectious cow. Furthermore, 30% of this exposure comes from infectivity residing in lymphatic and peripheral tissue that cannot be completely removed from a carcass.We are 95% confident that throughout Great Britain, no more than four sheep flocks currently harbour an ongoing BSE epidemic. However, since the exposure from a single infected sheep is high, the annual human exposure from four 'typical' BSE-infected flocks could be considerable. Small reductions in exposure could be achieved by strategies based on tissue testing, a 12-month age restriction or expanded definitions of high-risk tissues. A six-month age restriction is likely to be more effective and genotype-based strategies the most effective.

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“…Since sheep may also have been exposed to BSE-contaminated meat and bone meal (Butler, 1998) and BSE can be experimentally transmitted to sheep (Foster et al, 1993;Jeffrey et al, 2001;Houston et al, 2003), the possible human risk of consuming BSE-infected sheep meat has prompted research into this area.…”

mentioning

confidence: 99%