Sequential appearance and accumulation of pathognomonic markers in the central nervous system of hamsters orally infected with scrapie

Beekes, Michael; Baldauf, Elizabeth; Diringer, Heino

doi:10.1099/0022-1317-77-8-1925

Cited by 164 publications

(168 citation statements)

References 45 publications

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“…In light of the pertinent report by Rohwer (33), the sensitivity of the bioassay would appear unlikely to have been reduced -if at all -by more than 0.5 logs due to our method for the preparation of inocula. Therefore, the unexpectedly low infectivity titers found in muscle samples from our model animals may point to higher PrP Sc /infectivity ratios in the examined specimens than previously established for CNS tissue (3)(4). This explanation would also be consistent with the astonishingly low levels of infectivity measured in the M. triceps brachii despite the substantial amounts of PrP27-30 detected in that muscle.…”

Section: Time Course Of Prp Sc Deposition In Muscle Tissuesupporting

confidence: 72%

“…Apart from neuropathological features such as gliosis, neuronal cell loss, and spongiform change, these diseases are consistently characterized by the deposition in the CNS of a misfolded form of prion protein (PrP), which is known as PrP Sc (1). According to the prion hypothesis (2), the causative agents of TSEs (so-called "prions") are composed essentially of PrP Sc , and although the exact molecular structure of these pathogens remains elusive, there is substantial evidence that PrP Sc can be used as a reliable biochemical marker for TSE agents (3)(4)(5)(6). PrP Sc deposition in TSEs is not necessarily confined to the CNS; it has also been observed in a variety of peripheral tissues from donors with experimental and nonexperimental TSEs (1).…”

Section: Introductionmentioning

confidence: 99%

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Preclinical deposition of pathological prion protein PrPSc in muscles of hamsters orally exposed to scrapie

Thomzig¹,

Schulz‐Schaeffer²,

Kratzel³

et al. 2004

J. Clin. Invest.

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Recently, pathological prion protein PrP Sc , the putative key constituent of infectious agents causing transmissible spongiform encephalopathies (TSEs), was found in muscles of rodents experimentally infected with scrapie and in patients with Creutzfeldt-Jakob disease (CJD). For the assessment of risk scenarios originating from these findings (e.g., alimentary transmission of pathogens associated with bovine spongiform encephalopathy [BSE]

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Section: Time Course Of Prp Sc Deposition In Muscle Tissuesupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Preclinical deposition of pathological prion protein PrPSc in muscles of hamsters orally exposed to scrapie

Thomzig¹,

Schulz‐Schaeffer²,

Kratzel³

et al. 2004

J. Clin. Invest.

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show abstract

“…• per capita culling rate for cattle (not infected), µ • per capita birth rate, b • the reduction of infectious load by the rendering process, k 1 • the fraction of MBM that is fed to cattle (not to other animal species), k 2 • the fraction of infectious load from a non-BSE suspect carcass that enters the rendering process, c 1…”

Section: The Parametersmentioning

confidence: 99%

Quantifying BSE control by calculating the basic reproduction ratio R 0 for the infection among cattle

Koeijer¹,

Heesterbeek²,

Schreuder³

et al. 2004

Journal of Mathematical Biology

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Abstract. The safety of using meat and bone meal (MBM) in mammal feed was studied in view of BSE, by quantifying the risk of BSE transmission through different infection routes. This risk is embodied in the basic reproduction ratio R 0 of the infection, i.e. the average number of new infections induced by one initial infection. Only when R 0 is below 1, will the disease die out with certainty and the population will become free from BSE. Unfortunately this is a slow process due to the slow progression of the disease.We calculate R 0 explicitly from basic ingredients taking several different transmission routes into account. Several of the basic ingredients are functions of age or of infection-age. We also calculate the exponential growth rate r in terms of the same basic ingredients.Next we quantify the ingredients from available data and compute the effects on R 0 of various scenario's for controlling BSE, with examples for the UK and the Netherlands.

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“…[10][11][12] The importance of oral uptake of infectious material for transmission 12,29,30 and the contribution of lymphoid tissue related to the alimentary tract for local amplification of PrP sc , a conformational variant of prion protein (PrP), have been recognized 12,18 and is supported by experimental models. 3,4 Data indicate that scrapie generally follows oral uptake of prions and includes a preclinical phase characterized by local amplification of PrP sc in the lym-phoid tissue of the alimentary tract and transport through the peripheral nervous system into the central nervous system (CNS). 8,13,14 PrP sc accumulation patterns vary greatly among prion diseases, and susceptibility to scrapie is greatly modified by polymorphisms in the PrP gene, PRNP.…”

Section: Introductionmentioning

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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Sequential appearance and accumulation of pathognomonic markers in the central nervous system of hamsters orally infected with scrapie

Cited by 164 publications

References 45 publications

Preclinical deposition of pathological prion protein PrPSc in muscles of hamsters orally exposed to scrapie

Preclinical deposition of pathological prion protein PrPSc in muscles of hamsters orally exposed to scrapie

Quantifying BSE control by calculating the basic reproduction ratio R 0 for the infection among cattle

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

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Sequential appearance and accumulation of pathognomonic markers in the central nervous system of hamsters orally infected with scrapie

Cited by 164 publications

References 45 publications

Preclinical deposition of pathological prion protein PrPSc in muscles of hamsters orally exposed to scrapie

Preclinical deposition of pathological prion protein PrPSc in muscles of hamsters orally exposed to scrapie

Quantifying BSE control by calculating the basic reproduction ratio R 0 for the infection among cattle

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

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