In vitro amplification and detection of variant Creutzfeldt–Jakob disease PrPSc

Jones, Michael G. K.; Peden, Alexander; Prowse, C.; Gröner, Albrecht; Manson, Jean; Turner, M.; Ironside, James W.; MacGregor, Ian; Head, Mark W.

doi:10.1002/path.2204

Cited by 89 publications

(77 citation statements)

References 27 publications

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“…PMCA has been reported previously to increase the sensitivity of the detection of PrP Sc from brains of experimentally scrapie-infected rodents (Saborio et al, 2001;Bieschke et al, 2004;Deleault et al, 2003), cattle and sheep naturally infected with bovine spongiform encephalopathy and scrapie, respectively (Soto et al, 2005), and more recently from humans with Creutzfeldt-Jakob disease (Jones et al, 2007) and deer with chronic wasting disease (Kurt et al, 2007). Furthermore, the application of this technology for the detection of PrP Sc in blood, both at terminal stages of disease and in pre-symptomatic animals Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Reproduction of PrP c conversion in in vitro models has long been an area of investigation (Kocisko et al, 1994). Recently highly efficient conversion has been achieved in hamster models (Castilla et al, 2005a) and also using proteins derived from humans (Jones et al, 2007) and deers (Kurt et al, 2007) using a method involving protein misfolding cyclic amplification (PMCA). PMCA is a procedure first described by Saborio et al (2001) that facilitates rapid conversion of excess PrP c to PrP Sc following incubation in vitro.…”

Section: Introductionmentioning

confidence: 99%

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In vitro amplification of PrPSc derived from the brain and blood of sheep infected with scrapie

Thorne

Terry

2008

Journal of General Virology

101

116

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Scrapie is a fatal, naturally transmissible, neurodegenerative prion disease that affects sheep and goats and is characterized by the accumulation of a misfolded protein, PrPSc, converted from host-encoded PrPc, in the central nervous system of affected animals. Highly efficient in vitro conversion of host PrPc to PrPSc has been achieved in models of scrapie and in natural prion diseases by protein misfolding cyclic amplification (PMCA). Here, we demonstrate amplification, by serial PMCA, of PrPSc from individual sources of scrapie-infected sheep. Efficiency of amplification was affected by the pairing of the source of PrPSc with the control brain substrate of different genotypes of PrP. In line with previous studies, efficiency of amplification was greatly enhanced with the addition of a synthetic polyanion, polyadenylic acid (PolyA), facilitating rapid detection of low levels of PrPSc from body fluids such as blood. To this end PrPSc was amplified, in a 3 day PMCA assay, from blood leukocyte preparations from VRQ/VRQ scrapie-affected sheep at clinical end point. While PolyA-assisted PMCA resulted in spontaneous conversion of PrPc, we were able to distinguish blood samples from unaffected and affected sheep under controlled conditions. This study demonstrates that highly efficient amplification of PrPSc can be achieved for ovine scrapie from both brain and blood from naturally infected sheep and shows potential applications for improvements in current diagnostics and pre-mortem testing.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vitro amplification of PrPSc derived from the brain and blood of sheep infected with scrapie

Thorne

Terry

2008

Journal of General Virology

101

116

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“…PMCA was pioneered by Soto and colleagues 30 29 and is applicable to the high level amplification of natural sources of PrP Sc including ovine scrapie, bovine BSE, human CJD and cervid CWD. [31][32][33][34] Considering the in vivo dissemination of the prion agent for each prion strain/host combination, the prion diseases most likely to excrete prions are ovine scrapie, cervid CWD, experimental ovine BSE and human vCJD. To date, studies investigating the shedding of the prion agent have focused on ovine scrapie and cervid CWD and the excretion routes studied have included via urine, feces, milk, saliva, skin and within parturient material ( Table 1).…”

Section: Excretion Of Prionsmentioning

confidence: 99%

Prion transmission

Gough

Maddison

2010

Prion

123

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“…Although most of the work by Soto's group concerns a hamster model infected by strain 263K, significant amplification has been achieved with the PrP Sc produced by various mammalian species, including mice [47,72], sheep, goats and cattle [72], cervids [38] and humans [36]. The PrP Sc newly formed by PMCA has all the properties of the original PrP Sc , notably its infectious character [14,82].…”

Section: Protein Misfolding Cyclic Amplificationmentioning

confidence: 99%

Progress and limits of TSE diagnostic tools

et al. 2008

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-Following the two "mad cow" crises of 1996 and 2000, there was an urgent need for rapid and sensitive diagnostic methods to identify animals infected with the bovine spongiform encephalopathy (BSE) agent. This stimulated research in the field of prion diagnosis and led to the establishment of numerous so-called "rapid tests" which have been in use in Europe since 2001 for monitoring at-risk populations (rendering plants) and animals slaughtered for human consumption (slaughterhouse). These rapid tests have played a critical role in the management of the mad cow crisis by allowing the removal of prion infected carcasses from the human food chain, and by allowing a precise epidemiological monitoring of the BSE epizootic. They are all based on the detection of the abnormal form of the prion protein (PrP Sc or PrP res ) in brain tissues and consequently are only suitable for post-mortem diagnosis. Since it is now very clear that variant Creutzfeldt-Jakob disease (vCJD) can be transmitted by blood transfusion, the development of a blood test for the diagnosis of vCJD is a top priority. Although significant progress has been made in this direction, including the development of the protein misfolding cyclic amplification (PMCA) technology, at the time this paper was written, this objective had not yet been achieved. This is the most important challenge for the years to come in this field of prion research.

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In vitro amplification and detection of variant Creutzfeldt–Jakob disease PrP^Sc

Cited by 89 publications

References 27 publications

In vitro amplification of PrPSc derived from the brain and blood of sheep infected with scrapie

In vitro amplification of PrPSc derived from the brain and blood of sheep infected with scrapie

Prion transmission

Progress and limits of TSE diagnostic tools

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