PrPSc accumulation in myocytes from sheep incubating natural scrapie

Andréoletti, Olivier; Simon, Stéphanie; Lacroux, Caroline; Morel, Nathalie; Tabouret, Guillaume; Chabert, Armelle; Lugan, Séverine; Corbière, Fabien; Ferré, Pierre; Foucras, Gilles; Laude, Hubert; Eychenne, Francis; Grassi, Jacques; Schelcher, F.

doi:10.1038/nm1055

Cited by 122 publications

(102 citation statements)

References 11 publications

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“…This neuroinvasion apparently occurs via the enteric nervous system and its nerve fibres (Andreoletti et al, 2000;van Keulen et al, 2000), although haematogenous spread has also been proposed as a contributory/alternative route . From there the agent redistributes (centrifugally) to the peripheral nervous system and skeletal muscle (Andreoletti et al, 2004). In blood, infectivity and PrP Sc can be detected as early as at three months of age, and persist throughout the incubation period (Lacroux et al, 2012).…”

Section: Disease Pathogenesismentioning

confidence: 99%

Scientific Opinion on the scrapie situation in the EU after 10 years of monitoring and control in sheep and goats

Hald

Baggesen

2014

EFSA Journal

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To assess the effectiveness of the strategies implemented in the European Union (EU) to control Classical scrapie (CS), epidemiological data have been compared in the context of the efforts in terms of control measures applied over time. Official EU surveillance data and results from questionnaire surveys of EU Member States (MSs) have been used along with case studies. A spatio-temporal description of the occurrence of small ruminants TSEs in MSs in the period 2002-2012 is provided, with a particular focus on CS in sheep. Based on information collected from MSs, the potential effectiveness of breeding programmes for resistance to CS (BP-CS) in the dissemination of resistance into the general sheep population has been assessed for those countries for which the CS trend analysis has been performed. CS in sheep was reported in 17 MSs (average prevalence: 8.7 cases/10 000 tests), with heterogeneous trends and geographical distribution: among the 13 countries reporting a consistent number of cases, the trend analysis shows a statistically significant decreasing trend only for six of them. Variations in the implementation of genetic and non-genetic measures for the control of CS may explain the failure to improve the disease situation in the remaining seven MSs. At a national level, a reduction in CS seems to be linked to better-achieving BP-CSs. Control options applied to CS in sheep and goats indicate that a CS eradication policy that relies solely on the detection of infected flocks by post-mortem testing and subsequent depopulation would be unlikely to succeed. A minimum frequency of the ARR allele in a sheep population above which CS may be expected to fade-out could be estimated for each specific national sheep population. Recommendations for additional/alternative measures to control CS in sheep and goats are formulated. Scrapie situation in the EU EFSA Journal 2014;12 (7):3781 2 SUMMARYFollowing a request from the European Commission (EC), the EFSA Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific opinion on the scrapie situation in the European Union (EU) after 10 years of monitoring and control in sheep and goats. In particular, in order to evaluate the measures in place and assess the progress accomplished, the EC consulted EFSA to gain a better understanding of the dynamics of the epidemiological situation of Classical scrapie (CS) and Atypical scrapie (AS), and a retrospective analysis of the effectiveness of the control tools encompassed by EU legislation.The opinion provides background information in relation to CS and AS in sheep and goats, including information on the nature of the agents, genetic susceptibility of the hosts, transmission pathways and epidemiology of the diseases.Based on information from the EU TSE surveillance database, CS and AS in sheep and goats in the period 2002-2012 have been analysed to provide a spatio-temporal description of the occurrence of the diseases, after appropriate statistical adjustment accounting for the main known confounding factor...

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Section: Disease Pathogenesismentioning

confidence: 99%

Scientific Opinion on the scrapie situation in the EU after 10 years of monitoring and control in sheep and goats

Hald

Baggesen

2014

EFSA Journal

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“…To achieve this, we used a genetically modified mouse line that overexpresses the sheep VRQ allele and is considered to be highly effective in the detection of scrapie infectivity, demonstrated by the short incubation period observed after inoculation of brain homogenates from infected VRQ/VRQ or VRQ/ARQ sheep from the same flock (Telling et al 1995, Vilotte et al 2001. The tg338 mouse line has been proved to be able to detect infectivity in a tissue with less than 1/5000 brain infectivity, which is equivalent to sensitivity within the picogram range of Prp sc per milligram of tissue (Andreoletti et al 2004). Our results demonstrated that the transmission of scrapie did not occur with semen from infected rams at any point during scrapie incubation, even with a highly infected animal such as the oldest VRQ/VRQ ram that was sampled at the clinical stage and when spermatozoa and seminal plasma (and also cells and organelles that can be found within this fluid , Sutovsky et al 2007) contain undetectable levels of infectivity.…”

Section: Prpmentioning

confidence: 99%

Semen from scrapie-infected rams does not transmit prion infection to transgenic mice

Sarradin¹,

Melo²,

Barc³

et al. 2008

Reproduction

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Scrapie is the most common transmissible spongiform encephalopathy (TSE) in livestock. Natural contamination in sheep flocks is presumed to occur by maternal transmission to offspring. However, horizontal prion transmission from animal to animal exists and may be significant in sustaining and spreading contagion in the field. Artificial insemination is widely used in modern farming, and as large amounts of prion protein have been found in sheep sperm membrane, epididymal fluid and seminal plasma, horizontal transmission by this route was hypothesized since no clear information has been obtained on possible sexual transmission of TSE. We therefore tested the contamination levels of semen from scrapie-infected rams at different stages of incubation, including the clinical phase of the disease. We report here that under our experimental conditions ram semen did not transmit infectivity to scrapie-susceptible transgenic mice overexpressing the V 136 R 154 Q 171 allele of the sheep prion (PRNP) gene.These results suggest that artificial insemination and natural mating have a very low or negligible potential for the transmission of scrapie in sheep flocks.Reproduction (2008) 135 415-418

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“…28 This heterogeneity makes estimating the levels of PrP res in muscle difficult. However, in the positive muscle samples the signals obtained for 50 mg of muscle tissue were equivalent to 0.1 mg of vCJD brain (cerebral cortex) used as a positive control (Figures 1 to 3).…”

Section: Heterogeneous Distribution Of Prp Res In Skeletal Musclementioning

confidence: 99%

Detection and Localization of PrPSc in the Skeletal Muscle of Patients with Variant, Iatrogenic, and Sporadic Forms of Creutzfeldt-Jakob Disease

Peden

Ritchie

Head

et al. 2006

The American Journal of Pathology

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Variant Creutzfeldt-Jakob disease (vCJD) differs from other human prion diseases in that the pathogenic prion protein PrPSc can be detected to a greater extent at extraneuronal sites throughout the body, principally within lymphoid tissues. However, a recent study using a high-sensitivity Western blotting technique revealed low levels of PrP Sc in skeletal muscle from a quarter of Swiss patients with sporadic CJD (sCJD). This posed the question of whether PrP Sc in muscle could also be detected in vCJD, sCJD, and iatrogenic (iCJD) patients from other populations. Therefore, we have used the same high-sensitivity Western blotting technique, in combination with paraffin-embedded tissue blotting, to screen for PrP Sc

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PrPSc accumulation in myocytes from sheep incubating natural scrapie

Cited by 122 publications

References 11 publications

Scientific Opinion on the scrapie situation in the EU after 10 years of monitoring and control in sheep and goats

Scientific Opinion on the scrapie situation in the EU after 10 years of monitoring and control in sheep and goats

Semen from scrapie-infected rams does not transmit prion infection to transgenic mice

Detection and Localization of PrPSc in the Skeletal Muscle of Patients with Variant, Iatrogenic, and Sporadic Forms of Creutzfeldt-Jakob Disease

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