Scrapie epidemic in a fully PrP-genotyped sheep flock

Baylis, Matthew; Goldmann, Wilfred; Houston, Fiona; Cairns, D; Chong, Angela; Ross, Arlene; Smith, Allister; Hunter, Nora; McLean, Angela R.

doi:10.1099/0022-1317-83-11-2907

Cited by 75 publications

(73 citation statements)

References 13 publications

(26 reference statements)

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“…In the classical form, scrapie susceptibility is highly related to changes in speciϐic amino acids that leads to an altered form of the prion protein (PrP sc ). Polymorphisms in the host-encoded prion gene (PRNP) are major determinants of susceptibility to classic scrapie, with variations at codons 136, 154, and 171 conveying variable degrees of resistance (Baylis et al 2002). There are over 15 polymorphisms reported in PRNP (DeSilva et al 2003).…”

Section: Introductionmentioning

confidence: 99%

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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Section: Introductionmentioning

confidence: 99%

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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“…05) respectively. These relative susceptibility values are motivated by data on relative incidences [6,13]. However, we note that very recent estimates of the genotype-dependent risk of becoming a confirmed scrapie case for British sheep [14] yield very low risks for animals of the heterozygote genotypes VRQ/ARR (about 0 .…”

Section: Within-flock Transmission Modelmentioning

confidence: 94%

Epidemiological analysis of data for scrapie in Great Britain

2005

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SUMMARYIn recent years, the control or eradication of scrapie and any other transmissible spongiform encephalopathies (TSEs) possibly circulating in the sheep population has become a priority in Britain and elsewhere in Europe. A better understanding of the epidemiology of scrapie would greatly aid the development and evaluation of control and eradication strategies. Here we bound the range of key epidemiological parameters using a combination of relatively detailed pathogenesis and demography data, more limited data on susceptibility and incubation times, and recent survey data on scrapie incidence in Great Britain. These data are simultaneously analysed using mathematical models describing scrapie transmission between sheep and between flocks. Our analysis suggests that occurrence of scrapie in a flock typically provokes changes in flock management that promote termination of the outbreak, such as the adoption of selective breeding, and that a large fraction of cases (possibly over 80 %) goes undetected. We show that the data analysed are consistent with the within-flock reproduction number of scrapie lying in the range 1 . 5-6, consistent with previous epidemiological studies.

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“…b, c The spectral study was carried out along the white bar of 16.28 μm in length traced on the image. The correlation between the peaks of intensity at the yellow point revealed the close localisation of the labelled structures Gonzalez 2007) and (2) the genotype influences the susceptibility or resistance towards scrapie (Baylis et al 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Among the possible genotypes derivable from this combination, the ARR/ARR genotype is strongly associated with resistance to scrapie, whereas VRQ/VRQ is clearly associated with susceptibility (Baylis et al 2004). Depending on the breed of the sheep, the ARQ/ARQ genotype can be associated with resistance or with susceptibility, as in Suffolk (Hunter et al 1997) and Texel (Baylis et al 2002) breeds.…”

Section: Introductionmentioning

confidence: 99%

Neuroimmune connections in ovine pharyngeal tonsil: potential site for prion neuroinvasion

et al. 2012

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Recent studies have established the involvement of nasal-associated lymphoid tissues, mainly the pharyngeal tonsil, in prion pathogenesis. However, the mechanisms of the associated neuroinvasion are still debated. To determine potential sites for prion neuroinvasion inside the ovine pharyngeal tonsil, the topography of heavy (200 kDa) and light (70 kDa) neurofilaments and of glial fibrillar acidic protein has been semi-quantitatively analysed inside the various compartments of the tonsil. The results show that the most innervated areas are the interfollicular area and the connective tissue located beneath the respiratory epithelium. The existence of rare synapses between follicular dendritic cells and nerve fibres inside the germinal centre indicates that this mechanism of neuroinvasion is possible but, since germinal centres of lymphoid follicles are poorly innervated, other routes of neuroinvasion are likely. The host PRNP genotype does not influence the pattern of innervation in these various tonsil compartments, unlike ageing during which an increase of nerve endings occurs in a zone of high trafficking cells beneath the respiratory epithelium. A minimal age-related increase of innervation inside the lymphoid follicles has also been observed. An increase in nerve fibre density around the lymphoid follicles, in an area rich in mobile cells such as macrophages and dendritic cells capable of capturing and conveying pathogen prion protein (PrPd), might ensure more efficient infectivity, not in the early phase but in the advanced phase of lymphoinvasion after the amplification of PrPd; alternatively, this area might even act as a direct site of entry during neuroinvasion.

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Scrapie epidemic in a fully PrP-genotyped sheep flock

Cited by 75 publications

References 13 publications

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

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

Epidemiological analysis of data for scrapie in Great Britain

Neuroimmune connections in ovine pharyngeal tonsil: potential site for prion neuroinvasion

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