Genotype-dependent Molecular Evolution of Sheep Bovine Spongiform Encephalopathy (BSE) Prions in Vitro Affects Their Zoonotic Potential

Krejciova, Zuzana; Barria, Marcelo A.; Jones, Michael G. K.; Ironside, James W.; Jeffrey, Martin; González, Lorenzo; Head, Mark W.

doi:10.1074/jbc.m114.582965

Cited by 10 publications

(16 citation statements)

References 49 publications

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“…However, works by Castilla et al (38), Barria et al (36,39), Cassard et al (37), and others show that the species barrier may be more dynamic than previously estimated. It remains unknown whether natural passage of excreted CWD prions through generations of outbred cervids in nature may ultimately alter its species/transmission barrier.…”

Section: Figmentioning

confidence: 83%

“…Additional information is needed to assess the infectivity of excreta deposited in the environment; however, prion shedding of this magnitude in a free-ranging species would seem to pose a substantial challenge to eradication of CWD. The risk to humans and other species posed by florid dissemination of CWD prions into the environment, while unclear, cannot be discounted in light of more recent evidence that barriers to cross-species infection may not be absolute (36)(37)(38)(39). We have made significant progress in detection of prion amyloid seeding activity in excreta, saliva, and blood (11,14,27); however, assay inhibitors of these complex biological materials may yet remain.…”

Section: Discussionmentioning

confidence: 99%

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Longitudinal Detection of Prion Shedding in Saliva and Urine by Chronic Wasting Disease-Infected Deer by Real-Time Quaking-Induced Conversion

Henderson

Denkers

Hoover

et al. 2015

J Virol

108

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Chronic wasting disease (CWD) is an emergent, rapidly spreading prion disease of cervids. Shedding of infectious prions in saliva and urine is thought to be an important factor in CWD transmission. To help to elucidate this issue, we applied an in vitro amplification assay to determine the onset, duration, and magnitude of prion shedding in longitudinally collected saliva and urine samples from CWD-exposed white-tailed deer. We detected prion shedding as early as 3 months after CWD exposure and sustained shedding throughout the disease course. We estimated that the 50% lethal dose (LD 50 ) for cervidized transgenic mice would be contained in 1 ml of infected deer saliva or 10 ml of urine. Given the average course of infection and daily production of these body fluids, an infected deer would shed thousands of prion infectious doses over the course of CWD infection. The direct and indirect environmental impacts of this magnitude of prion shedding on cervid and noncervid species are surely significant. IMPORTANCEChronic wasting disease (CWD) is an emerging and uniformly fatal prion disease affecting free-ranging deer and elk and is now recognized in 22 U.S. states and 2 Canadian provinces. It is unique among prion diseases in that it is transmitted naturally through wild populations. A major hypothesis to explain CWD's florid spread is that prions are shed in excreta and transmitted via direct or indirect environmental contact. Here we use a rapid in vitro assay to show that infectious doses of CWD prions are in fact shed throughout the multiyear disease course in deer. This finding is an important advance in assessing the risks posed by shed CWD prions to animals as well as humans. Chronic wasting disease (CWD) is an emergent transmissible spongiform encephalopathy affecting free-ranging populations of mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus), elk (Cervus canadensis), and moose (Alces alces) in North America (1, 2). CWD is the only known prion disease to spread horizontally through wild populations, in which it continues to expand in prevalence and range in North America (3). As a prion disease, CWD is caused by a pathogenic, misfolded conformation of the normal, natively folded cellular protein PrP C to a pathogenic prion conformer (variously designated PrP CWD , PrP SC , or PrP D ) (2, 4-7). A leading hypothesis for the facile spread of CWD in wild populations is that the accumulation and excretion of CWD prions in bodily fluids facilitate both direct animal-to-animal transfer and substantial environmental contamination leading to indirect infection (8-10). Infectious CWD prions have been identified in urine, saliva, blood, and feces by bioassay of deer or cervid PrP Cexpressing transgenic mice (11-16). Prions bound to soil are remarkably stable, retaining infectivity even after a decade (9,(17)(18)(19)(20). Moreover, some evidence suggests that prions bound to soil may increase infectivity through an unknown mechanism (21). Understanding the kinetics and magnitude of C...

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Section: Figmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Longitudinal Detection of Prion Shedding in Saliva and Urine by Chronic Wasting Disease-Infected Deer by Real-Time Quaking-Induced Conversion

Henderson

Denkers

Hoover

et al. 2015

J Virol

108

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“…Notwithstanding the importance of small and large animal models to our understanding of the pathobiology of prion diseases, there is an urgent need for complementary experimental systems to model aspects of human prion diseases ( Jones et al, 2011 ; McCutcheon et al, 2011 ; Watts and Prusiner, 2014 ). In this regard, cell-free assays have provided important insights into prion composition, prion strains, and barriers to prion transmission ( Wang et al, 2010 ; Deleault et al, 2012 ; Krejciova et al, 2014a ). Against this background, the availability of a scalable and physiologically relevant human-based cellular experimental system to study human prion diseases—including the modeling of neuronal–glial interactions that are increasingly thought to be involved in neurodegenerative diseases—would be of great value ( Gómez-Nicola et al, 2013 ; Asuni et al, 2014 ; Hennessy et al, 2015 ; Liddelow et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Human stem cell–derived astrocytes replicate human prions in a PRNP genotype–dependent manner

Krejciova

Alibhai

Zhao

et al. 2017

Journal of Experimental Medicine

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“…As seen in vivo the strain and source of PrP Sc , in particular the PRNP genotype of seed and substrate, has a clear influence on the amplification pattern obtained by PMCA (Bucalossi et al, 2011;Thorne et al, 2012;Krejciova et al, 2014;Priem et al, 2014). In this regard it is of interest that a switch of the conversion profile has been shown by the amplification of an ARR scrapie isolate in different sheep genotypes, which resulted in a conversion profile that resembled mostly that of ARQ scrapie (Bucalossi et al, 2011;Priem et al, 2014).…”

Section: Pmca Was Developed In 2001 As a Technique For The In Vitro Amentioning

confidence: 99%

“…On the other hand, ovine BSE and cattle BSE prions, amplified in an ARQ substrate, retained their molecular characteristics. However this PMCA product contained an additional scrapie-like component (Krejciova et al, 2014).…”

Section: Pmca Was Developed In 2001 As a Technique For The In Vitro Amentioning

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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Genotype-dependent Molecular Evolution of Sheep Bovine Spongiform Encephalopathy (BSE) Prions in Vitro Affects Their Zoonotic Potential

Cited by 10 publications

References 49 publications

Longitudinal Detection of Prion Shedding in Saliva and Urine by Chronic Wasting Disease-Infected Deer by Real-Time Quaking-Induced Conversion

Longitudinal Detection of Prion Shedding in Saliva and Urine by Chronic Wasting Disease-Infected Deer by Real-Time Quaking-Induced Conversion

Human stem cell–derived astrocytes replicate human prions in a PRNP genotype–dependent manner

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

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