Experimental transmission of atypical scrapie to sheep

Simmons, Marion; Konold, Timm; Simmons, Hugh; Spencer, Y. I.; Lockey, Richard; Spiropoulos, John; Everitt, Sharon; Clifford, Derek

doi:10.1186/1746-6148-3-20

Cited by 85 publications

(106 citation statements)

References 22 publications

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“…So far, three distinct strains have been identified in the sheep and two of them stably passaged in the natural host: SSBP/1 (originating from the scrapie Cheviot sheep pool brain, [68]), CH1641 (isolated from a UK Cheviot sheep in the 1970s', [74]) and atypical scrapie [183].…”

Section: Strain Diversity In the Natural Hostmentioning

confidence: 99%

Prion agent diversity and species barrier

2008

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-Mammalian prions are the infectious agents responsible for transmissible spongiform encephalopathies (TSE), a group of fatal, neurodegenerative diseases, affecting both domestic animals and humans. The most widely accepted view to date is that these agents lack a nucleic acid genome and consist primarily of PrP Sc , a misfolded, aggregated form of the host-encoded cellular prion protein (PrP C ) that propagates by autocatalytic conversion and accumulates mainly in the brain. The BSE epizooty, allied with the emergence of its human counterpart, variant CJD, has focused much attention on two characteristics that prions share with conventional infectious agents. First, the existence of multiple prion strains that impose, after inoculation in the same host, specific and stable phenotypic traits such as incubation period, molecular pattern of PrP Sc and neuropathology. Prion strains are thought to be enciphered within distinct PrP Sc conformers. Second, a transmission barrier exists that restricts the propagation of prions between different species. Here we discuss the possible situations resulting from the confrontation between species barrier and prion strain diversity, the molecular mechanisms involved and the potential of interspecies transmission of animal prions, including recently discovered forms of TSE in ruminants.prion / strain / misfolding / species barrier / PrP Table of Mammalian prion diseases or transmissible spongiform encephalopathies (TSE) form a group of related, invariably fatal neurodegenerative disorders of both animals and humans. The brain pathology consists of spongiosis, astrocytosis, neuronal loss and neural tissue from affected individuals contains an infectious agent, the prion, setting these diseases apart from other neurodegenerative diseases. Prion replication is thought to involve in essence the self-perpetuating conversion of the host-encoded cellular prion protein (PrP C ) into a misfolded form (PrP Sc ) that tends to aggregate and may be neurotoxic (for reviews [1,157]). Prion replication may also occur in lymphoid tissues but is there poorly if not pathogenic (for review [126], [133]). PrP C is a protein with two variably occupied glycosylation sites. It is attached at the outer of the plasma membrane by a glycosylphosphatidylinositol anchor. Its secondary structure is rich in alpha-helix and the protein is likely to be in a monomeric state in mild detergents. While its precise physiological function has not been assigned, PrP C is essential for prion replication and neurotoxicity to occur [57,129]. Upon infection, PrP C is refolded -without apparent post-translational modification -into beta-sheet -rich PrP Sc , initially in the presence of exogenous PrP Sc and then by an autocatalytic process. It leads to the formation of aggregates, sometimes of amyloid type, that can be differentiated from PrP C because of their partial resistance to protease digestion and of their insolubility into non-denaturing detergents [153]. Proteinase K, the most commonly used protease, di...

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Section: Strain Diversity In the Natural Hostmentioning

confidence: 99%

Prion agent diversity and species barrier

2008

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“…In 2012 and 2013, it was found in *0.1 % of the w18 000 sheep which were tested in abattoir and fallenstock surveys each year (Ortiz-Pelaez & Arnold, 2013). Atypical scrapie is not thought to be naturally transmissible, although successful experimental transmissions have been achieved in sheep and transgenic mice; in the latter with similar pathology to that seen in the original sheep (Andréoletti et al, 2011;Le Dur et al, 2005;Simmons et al, 2007Simmons et al, , 2010.…”

Section: Introductionmentioning

confidence: 99%

Archival search for historical atypical scrapie in sheep reveals evidence for mixed infections

Chong

Kennedy

Goldmann

et al. 2015

Journal of General Virology

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“…It was demonstrated that the placenta shed from goats with classical scrapie can transmit the disease to susceptible goat kids and lambs . Intracerebral transmissibility of the atypical/Nor98 agent has been demonstrated in rodent models (transgenic animals expressing the ovine PRNP), sheep and primate (Simmons et al, 2007 andGötte et al, 2011;Comoy et al, 2015). Experimental oral transmission of atypical scrapie showed that sheep carried AHQ/AHQ genotype developed the disease .…”

Section: Transmission Routes In Scrapiementioning

confidence: 99%

Review: A review on classical and atypical scrapie in caprine: Prion protein gene polymorphisms and their role in the disease

Curcio

Sebastiani

Lorenzo

et al. 2016

Animal

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Scrapie is a naturally occurring transmissible spongiform encephalopathy in sheep and goat. It has been known for~250 years and is characterised by the accumulation of an abnormal isoform of a host-encoded prion protein that leads to progressive neurodegeneration and death. Scrapie is recognised in two forms, classical and atypical scrapie. The susceptibility to both types of scrapie is influenced by polymorphisms of the prion protein gene (PRNP). Sheep susceptibility or resistance to classical scrapie is strongly regulated by the polymorphisms at codons 136, 154 and 171 of the PRNP. The genetic role in atypical scrapie in sheep has been defined by polymorphisms at codons 141, 154 and 171, which are associated with different degrees of risk in the occurrence of the ovine disease. Progress has been achieved in the prevention of scrapie in sheep due to efficient genetic breeding programmes based on eradication and control of the disease. In Europe, the success of these programmes has been verified by applying eradication and genetic selection plans. In general terms, the ovine selection plans aim to eliminate and reduce the susceptible allele and to enrich the resistant allele ARR. During outbreaks all susceptible animals are slaughtered, only ARR/ARR resistant rams and sheep and semi-resistant females are preserved. In the occurrence of scrapie positive goats a complete cull of the flock (stamping out) is performed with great economic loss and severe risk of extinction for the endangered breeds. The ability to select scrapie-resistant animals allows to define new breeding strategies aimed to boost genetic progress while reducing costs during scrapie outbreaks. Allelic variants of PRNP can be protective for caprine scrapie, and the knowledge of their distribution in goats has become very important. Over the past few years, the integration of genetic information on goat populations could be used to make selection decisions, commonly referred to as genetic selection. The objective of this review was to summarise the main findings of polymorphisms of the caprine prion protein (PrP) gene and to discuss the possible application of goat breeding schemes integrating genetic selection, with their relative advantages and limitations.

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Experimental transmission of atypical scrapie to sheep

Cited by 85 publications

References 22 publications

Prion agent diversity and species barrier

Prion agent diversity and species barrier

Archival search for historical atypical scrapie in sheep reveals evidence for mixed infections

Review: A review on classical and atypical scrapie in caprine: Prion protein gene polymorphisms and their role in the disease

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