Prions Are Secreted into the Oral Cavity in Sheep with Preclinical Scrapie

Maddison, Ben C.; Rees, Helen C.; Baker, Claire A.; Taema, Maged M.; Bellworthy, S. J.; Thorne, Leigh; Terry, Linda A.; Gough, Kevin C.

doi:10.1086/652457

Cited by 60 publications

(54 citation statements)

References 13 publications

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“…Thus, the peroral and perenteral prion transmission is of greatest consequence with respect to TSE disease establishment. Moreover, the presence of PrP Sc in the buccal cavity of scrapie-infected sheep 10 (reviewed in ref. 11) and the possible horizontal transfer as a result hereof, as may be similarly proposed for animals suffering from other TSEs, may further contribute to the oral transmissibility of TSEs.…”

Section: Alimentary Prion Infectionsmentioning

confidence: 99%

Alimentary prion infections

Dias

Jovanović²,

Weiß³

2011

Prion

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N eurodegenerative diseases are caused by proteinaceous aggregates, usually consisting of misfolded proteins which are often typified by a high proportion of β-sheets that accumulate in the central nervous system. These diseases, including Morbus Alzheimer, Parkinson disease and Transmissible Spongiform Encephalopathies (TSEs)-also termed prion disorders-afflict a substantial proportion of the human population and, as such, the etiology and pathogenesis of these diseases has been the focus of mounting research. Although many of these diseases arise from genetic mutations or are sporadic in nature, the possible horizontal transmissibility of neurodegenerative diseases poses a great threat to population health. In this article we discuss recent studies that suggest that the "non-transmissible" status bestowed upon Alzheimer and Parkinson diseases may need to be revised as these diseases have been successfully induced through tissue transplants. Furthermore, we highlight the importance of investigating the "natural" mechanism of prion transmission including peroral and perenteral transmission, proposed routes of gastrointestinal uptake and neuroinvasion of ingested infectious prion proteins. We examine the multitude of factors which may influence oral transmissibility and discuss the zoonotic threats that Chronic Wasting disease (CWD), Bovine Spongiform Encephalopathy (BSE) and Scrapie may pose resulting in vCJD or related disorders. In addition, we suggest that the 37 kDa/67 kDa laminin receptor on the cell surface of enterocytes, a major cell population in

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Section: Alimentary Prion Infectionsmentioning

confidence: 99%

Alimentary prion infections

Dias

Jovanović²,

Weiß³

2011

Prion

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“…In sheep with preclinical, natural scrapie infections, sPMCA facilitated the detection of PrP Sc within buccal swabs throughout most of the incubation period of the disease with an apparent peak in prion secretion around the mid-term of disease progression. 70 The amounts of prion present in saliva are likely to be low as indicated by CWD-infected saliva producing prolonged incubation periods and incomplete attack rates within the transgenic mouse bioassay. 41 …”

Section: Secretion Of Prions Within Milkmentioning

confidence: 99%

Prion transmission

Gough

Maddison

2010

Prion

119

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“…Samples contained in sealed 0.2-ml PCR tubes were placed in an ultrasonicating water bath (model S4000; Misonix) at 37°C, and sonications were performed for 40 s at 200 W. Sonications were repeated once every 30 min for 24 h (1 PMCA round), after which the amplified samples were diluted 1 in 3 with PMCA substrate in a final volume of 100 l and the sample was subjected to additional rounds of PMCA. In the present study, the brain homogenate substrate required between five and nine rounds of sPMCA to achieve the same levels of amplification that had previously been achieved at round three or four with a different brain substrate (17). This estimation of the level of amplification efficiency between substrates was carried out using buccal extracts from VRQ/VRQ sheep.…”

Section: Methodsmentioning

confidence: 84%

“…Four swabs were collected from each animal at single time points and, as such, provide a snapshot of the likely presence of prions in the oral cavity. Two buccal swab samples were processed using a silicon dioxide (SiO 2 ) enrichment step as previously described (17,22). The SiO 2 -extracted material was then centrifuged for 3 min at 16,000 ϫ g, and the supernatant was diluted 1:10 in PMCA brain homogenate substrate (10% [wt/vol]) from a VRQ/ VRQ PRNP genotype animal (in phosphate-buffered saline [PBS]), 150 mmol/liter NaCl, 4 mmol/liter EDTA, pH 8.0, 1% (wt/vol) Triton X-100, and mini-protease inhibitor (Roche) to a final volume of 100 l. All buccal samples were amplified in this single substrate, as positive buccal swab extracts were amplified most efficiently within VRQ/VRQ substrate rather than the homologous heterozygous substrate (data not presented).…”

Section: Methodsmentioning

confidence: 99%

“…Prions were detected using an in vitro prion protein amplification technique known as serial protein misfolding cyclic amplification (sPMCA), a methodology conceptually analogous to nucleic acid amplification by PCR (23). Amplifiable prion material was detected in buccal swabs from exposed sheep from 9 months of age to the appearance of clinical disease in animals with a VRQ/VRQ PRNP genotype (17). It is likely that oral prion availability highlights an important factor in the horizontal spread of scrapie, both by direct sheep-to-sheep transmission of disease and via contribution to reservoirs of infectivity in the farm environ-ment, including fomites (15).…”

mentioning

confidence: 99%

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The Oral Secretion of Infectious Scrapie Prions Occurs in Preclinical Sheep with a Range of PRNP Genotypes

Gough

Baker

Rees

et al. 2012

J Virol

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Preclinical sheep with the highly scrapie-susceptible VRQ/VRQ PRNP genotype secrete prions from the oral cavity. In order to further understand the significance of orally available prions, buccal swabs were taken from sheep with a range of PRNP genotypes and analyzed by serial protein misfolding cyclic amplification (sPMCA). Prions were detected in buccal swabs from scrapie-exposed sheep of genotypes linked to high (VRQ/VRQ and ARQ/VRQ) and low (ARR/VRQ and AHQ/VRQ) lymphoreticular system involvement in scrapie pathogenesis. For both groups, the level of prion detection was significantly higher than that for scrapie-resistant ARR/ARR sheep which were kept in the same farm environment and acted as sentinel controls for prions derived from the environment which might contaminate the oral cavity. In addition, sheep with no exposure to the scrapie agent did not contain any measurable prions within the oral cavity. Furthermore, prions were detected in sheep over a wide age range representing various stages of preclinical disease. These data demonstrate that orally available scrapie prions may be a common feature in sheep incubating scrapie, regardless of the PRNP genotype and any associated high-level accumulation of PrP Sc within lymphoreticular tissues. PrP Sc was present in buccal swabs from a large proportion of sheep with PRNP genotypes associated with relatively low disease penetrance, indicating that subclinical scrapie infection is likely to be a common occurrence. The significance of positive sPMCA reactions was confirmed by the transmission of infectivity in buccal swab extracts to Tg338 mice, illustrating the likely importance of orally available prions in the horizontal transmission of scrapie.

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Prions Are Secreted into the Oral Cavity in Sheep with Preclinical Scrapie

Cited by 60 publications

References 13 publications

Alimentary prion infections

Alimentary prion infections

Prion transmission

The Oral Secretion of Infectious Scrapie Prions Occurs in Preclinical Sheep with a Range of PRNP Genotypes

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