Kuru prions and sporadic Creutzfeldt–Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice

Wadsworth, Jonathan D. F.; Joiner, Susan; Linehan, Jacqueline M.; Desbruslais, Melanie; Fox, Katie; Cooper, Stephen R.; Cronier, Sabrina; Asante, Emmanuel A.; Mead, Simon; Brandner, Sebastian; Hill, Andrew F.; Collinge, John

doi:10.1073/pnas.0800190105

Cited by 71 publications

(136 citation statements)

References 81 publications

(154 reference statements)

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“…The peripheral pathogenesis of vCJD differs significantly from that of classical CJD, inherited prion disease, and kuru, with disease-related PrP (PrP Sc ) being uniformly and prominently detected in a range of lymphoreticular tissues at autopsy [33][34][35][36][37]. To date, antemortem tonsil biopsy has shown 100% sensitivity and specificity for diagnosis of clinical vCJD [30,33,34], and the fact that lymphoreticular prion infection is not a feature of iatrogenic CJD [33,36] or kuru [21,38] argues that the distinct pathogenesis of vCJD relates to the effect of prion strain rather than to a peripheral route of infection [21,38,39]. Because lymphoreticular colonization is thought to precede neuroinvasion in vCJD, and indeed has been detected in archived surgical samples removed prior to the development of overt clinical symptoms [40,41], anonymous screening of lymphoreticular tissues removed during routine surgery appears to offer a practical means to estimate the population prevalence of asymptomatic vCJD infection.…”

Section: Introductionmentioning

confidence: 99%

“…Transgenic modelling has provided a molecular explanation for these findings by showing that human PrP 129 valine is unable to propagate the vCJD prion strain [51] and that BSE-or vCJD-challenged human PrP 129V transgenic mice propagate novel prion strains that have not yet been identified in humans [3,39,51]. It is unclear whether humans of the PRNP 129VV genotype following infection with BSE prions would develop a clinical disease and if so, what clinicopathological phenotype would result [7,8,51].…”

Section: Introductionmentioning

confidence: 99%

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Effect of fixation on brain and lymphoreticular vCJD prions and bioassay of key positive specimens from a retrospective vCJD prevalence study

Wadsworth

Dalmau-Mena

Joiner

et al. 2010

The Journal of Pathology

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Anonymous screening of lymphoreticular tissues removed during routine surgery has been applied to estimate the UK population prevalence of asymptomatic vCJD prion infection. The retrospective study of Hilton et al (J Pathol 2004; 203: 733-739) found accumulation of abnormal prion protein in three formalin-fixed appendix specimens. This led to an estimated UK prevalence of vCJD infection of ∼1 in 4000, which remains the key evidence supporting current risk reduction measures to reduce iatrogenic transmission of vCJD prions in the UK. Confirmatory testing of these positives has been hampered by the inability to perform immunoblotting of formalin-fixed tissue. Animal transmission studies offer the potential for 'gold standard' confirmatory testing but are limited by both transmission barrier effects and known effects of fixation on scrapie prion titre in experimental models. Here we report the effects of fixation on brain and lymphoreticular human vCJD prions and comparative bioassay of two of the three prevalence study formalin-fixed, paraffin-embedded (FFPE) appendix specimens using transgenic mice expressing human prion protein (PrP). While transgenic mice expressing human PrP 129M readily reported vCJD prion infection after inoculation with frozen vCJD brain or appendix, and also FFPE vCJD brain, no infectivity was detected in FFPE vCJD spleen. No prion transmission was observed from either of the FFPE appendix specimens. The absence of detectable infectivity in fixed, known positive vCJD lymphoreticular tissue precludes interpreting negative transmissions from vCJD prevalence study appendix specimens. In this context, the Hilton et al study should continue to inform risk assessment pending the outcome of larger-scale studies on discarded surgical tissues and autopsy samples.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of fixation on brain and lymphoreticular vCJD prions and bioassay of key positive specimens from a retrospective vCJD prevalence study

Wadsworth

Dalmau-Mena

Joiner

et al. 2010

The Journal of Pathology

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“…It has been proposed that kuru originated from the consumption of brain tissue from a tribe member who had died with sCJD; this has been supported by the findings of transmission studies of kuru and sCJD to transgenic and wild-type mice (Wadsworth et al 2008). Kuru declined after this ritual was discouraged in the 1960s and is now extinct.…”

Section: Acquired Human Prion Diseases Kurumentioning

confidence: 61%

Sporadic and Infectious Human Prion Diseases

Will

Ironside

2016

Cold Spring Harb Perspect Med

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“…The disease died out with the cessation of these rituals and hence is not created spontaneously by the human host. Wadsworth et al (2008) demonstrated that kuru prions have prion strain properties equivalent to those of classical (sporadic and iatrogenic) CJD prions and speculated that kuru may have originated from chance consumption of an individual with sCJD. However data from Manuelidis et al (2009) indicate that the kuru agent is a unique geographic isolate unrelated to sCJD.…”

Section: Agent Strains In Humansmentioning

confidence: 99%

Scientific Opinion on a request for a review of a scientific publication concerning the zoonotic potential of ovine scrapie prions

2015

EFSA Journal

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The factors that modulate the transmissibility of Transmissible Spongiform Encephalopathies (TSE) and the approaches for the study of their zoonotic potential are reviewed. The paper 'Evidence for zoonotic potential of ovine scrapie prions' by Cassard et al. (2014) is scientifically appraised, focussing on the experimental design, the results and the conclusions. The paper provides evidence in a laboratory experiment that some Classical scrapie isolates can propagate in humanised transgenic mice and produce prions that on second passage are similar to those causing one form of sporadic Creutzfeldt-Jakob disease (sCJD). It is concluded that the results from the study raise the possibility that scrapie prions have the potential to be zoonotic, but do not provide evidence that transmission can or does take place under field conditions. The conclusions of the 2011 ECDC-EFSA 'Joint Scientific Opinion on any possible epidemiological or molecular association between TSEs in animals and humans' are reviewed in the light of the new scientific evidence available since its publication. This supports and strengthens the conclusions of that opinion with regard to the potential for some animal TSE to be zoonotic, but does not provide evidence of a causal link between Classical or Atypical scrapie and human TSE. Current evidence does not establish this link, and no consistent risk factors have been identified for sCJD. The possibility of scrapie-related public health risks from the consumption of ovine products cannot be assessed. Recommendations are formulated on further studies and data that are needed to investigate the zoonotic potential of animal TSE and to estimate the amount of infectivity from TSE-infected products sourced from small ruminants and entering the food chain in the European Union. © European Food Safety Authority, 2015Keywords: Atypical scrapie, Classical scrapie, Creutzfeldt-Jakob disease, transmissible spongiform encephalopathy, zoonosis Amendment: An amendment has been made to the following sentence on p. 31: 'In this regard the emergence of sCJD is not so surprising, and has been described after inoculation of tgHu mice with cattle BSE and human vCJD (Asante et al., 2002;Beringue et al., 2008b)'. This was carried out to clarify that one of the references reported emergence of sporadic CJD after experimental inoculation of humanised transgenic mice with vCJD, which was not correctly stated in the published opinion. An amendment has been made on p. 28, to add the word 'OR' between two search terms within the literature search string reported. Reproduction is authorised provided the source is acknowledged. Requestor: European CommissionThe EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. SummaryFollowing a request from the European Commission (EC), the EFSA Panel on Biological Hazards (BIOHAZ Panel) was asked to deliver a scientific opinion on the review of a scientific publication concerning the zoonotic potential of ovine scrapie prions.T...

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Kuru prions and sporadic Creutzfeldt–Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice

Cited by 71 publications

References 81 publications

Effect of fixation on brain and lymphoreticular vCJD prions and bioassay of key positive specimens from a retrospective vCJD prevalence study

Effect of fixation on brain and lymphoreticular vCJD prions and bioassay of key positive specimens from a retrospective vCJD prevalence study

Sporadic and Infectious Human Prion Diseases

Scientific Opinion on a request for a review of a scientific publication concerning the zoonotic potential of ovine scrapie prions

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