Atypical/Nor98 scrapie: properties of the agent, genetics, and epidemiology

Benestad, Sylvie L.; Arsac, Jean-Noël; Goldmann, Wilfred; Nöremark, Maria

doi:10.1051/vetres:2007056

Cited by 213 publications

(297 citation statements)

References 40 publications

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“…PrP genotypes of the donor animals (sheep and goat) did not notably influence the incubation time either. Further analyses demonstrated that all the atypical cases transmitted so far involve a unique strain, closely related if not identical to that present in Nor98 cases that were discovered earlier on in Norway ( [17,18,119] and our unpublished data). Notably, this strain exhibits fairly high infectious titre, including in ARR-homozygous sheep [119].…”

Section: Assessment Of Scrapie Strain Diversity With Transgenic Mousesupporting

confidence: 57%

“…The abnormal PrP associated with these atypical cases is characterized by a lower resistance to protease digestion as compared to classical scrapie. Furthermore, confirmatory neuropathological methods were often inconclusive [18]. Atypical scrapie has been diagnosed in sheep carrying various PrP genotypes, including those homozygous for ARR [40,137,141].…”

Section: Tse In Sheep and Goatsmentioning

confidence: 99%

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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: Assessment Of Scrapie Strain Diversity With Transgenic Mousesupporting

confidence: 57%

Section: Tse In Sheep and Goatsmentioning

confidence: 99%

Prion agent diversity and species barrier

2008

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“…The atypical scrapie form Nor98 (Benestad et al 2008), associated with the variation L141F, has not been described in Brazil. In our work we have found all animals to be of the L/L homozygous genotype.…”

Section: Resultsmentioning

confidence: 96%

Single nucleotide polymorphisms at 15 codons of the prion protein gene from a scrapie-affected herd of Suffolk sheep in Brazil

et al. 2011

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Scrapie is a transmissible spongiform encephalopathy of sheeps and goats, associated with the deposition of a isoform of the prion protein (PrPsc). This isoform presents an altered conformation that leads to aggregation in the host's central nervous and lymphoreticular systems. Predisposition to the prion agent infection can be influenced by specific genotypes related to mutations in amino acids of the PrPsc gene. The most characterized mutations occur at codons 136, 154 and 171, with genotypes VRQ being the most susceptible and ARR the most resistant. In this study we have analyzed polymorphisms in 15 different codons of the PrPsc gene in sheeps from a Suffolk herd from Brazil affected by an outbreak of classical scrapie. Amplicons from the PrPsc gene, encompassing the most relevant altered codons in the protein, were sequenced in order to determine each animal's genotype. We have found polymorphisms at 3 of the 15 analyzed codons (136, 143 and 171). The most variable codon was 171, where all described alleles were identified. A rare polymorphism was found at the 143 codon in 4% of the samples analyzed, which has been described as increasing scrapie resistance in otherwise susceptible animals. No other polymorphisms were detected in the remaining 12 analyzed codons, all of them corresponding to the wild-type prion protein. Regarding the risk degree of developing scrapie, most of the animals (96%) had genotypes corresponding to risk groups 1 to 3 (very low to moderate), with only 4% in the higher risks group. Our data is discussed in relation to preventive measures involving genotyping and positive selection to control the disease.

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“…The details of PrP genetics in atypical scrapie are presented in the special issue ("Prion diseases in animals") by Benestad et al [10]. However, it is important to highlight here some of the genetic differences between classical and atypical scrapie which are the topic of current TSE research.…”

Section: Atypical Scrapie In Sheepmentioning

confidence: 99%

PrPgenetics in ruminant transmissible spongiform encephalopathies

2008

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-Scrapie, bovine spongiform encephalopathy (BSE), and chronic wasting disease (CWD) are prion diseases in ruminants with considerable impact on animal health and welfare. They can also pose a risk to human health and control is therefore an important issue. Prion protein (PrP) genetics may be used to control and eventually eradicate animal prion diseases. The PrP gene in sheep and other representatives of the order Artiodactyles has many polymorphisms of which several are crucial determinants of susceptibility to prion diseases, also known as transmissible spongiform encephalopathies (TSE). This review will present the current understanding of PrP genetics in ruminants highlighting similarity and difference between the species in the context of TSE.

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Atypical/Nor98 scrapie: properties of the agent, genetics, and epidemiology

Cited by 213 publications

References 40 publications

Prion agent diversity and species barrier

Prion agent diversity and species barrier

Single nucleotide polymorphisms at 15 codons of the prion protein gene from a scrapie-affected herd of Suffolk sheep in Brazil

PrPgenetics in ruminant transmissible spongiform encephalopathies

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