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Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of CWD TSE PRION

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Feb 27, 2006
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Subject: PRION 2017 CONFERENCE ABSTRACT First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress

First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress

Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1

University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen

This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves.

Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice.

At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.


TUESDAY, JUNE 13, 2017

PRION 2017 CONFERENCE ABSTRACT Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD

http://chronic-wasting-disease.blogspot ... ronic.html

P55 Susceptibility of human prion protein to in vitro conversion by chronic wasting disease prions

Dr Marcelo Barria1, Adriana Libori1, Dr Gordon Mitchell2, Dr Mark Head1
1National CJD Research & Surveillance Unit, Centre For Clinical Brain Sciences, The University Of Edinburgh, Edinburgh, United Kingdom, 2National and OlE Reference Laboratory for Scrapie and CWD, Ottawa Laboratory Fallowfield, Canadian Food Inspection Agency, Ottawa, Canada

Prion diseases are fatal neurodegenerative conditions occurring in humans as sporadic, genetic and acquired forms. In animals, the majority of prion diseases are acquired. Some animal prion diseases, such as scrapie in sheep are generally considered to be of no or only very low risk to human health. In contrast, bovine spongiform encephalopathy (BSE) is a known zoonotic prion disease strain. The zoonotic status of chronic wasting disease (CWD), a prion disease of cervids, remains poorly quantified. At present CWD has been recognised as a problem in both farmed and wild cervids species in USA, Canada, South Korea, and very recently has been recognised in reindeer in Europe.

Aim: The aim of this work is to determine whether CWD prions from elk, white tailed deer and caribou (reindeer) are able to convert the human prion protein to the disease-associated form.

Methods: We have used a cell-free seeded protein misfolding assay, protein misfolding cyclic amplification or PMCA, to test for conversion of the human prion protein by elk, white tailed deer and caribou (reindeer) PrPSc in a single round of amplification. Any misfolded human PrP protein (PrPres) is sensitively detected by Western blot using the 3F4 antibody.

Results: Amplification reactions seeded with Prnp codon 132 MM elk CWD brain in humanised 129 MM transgenic mouse brain substrate were able to produce human PrPres. However, the heterozygous (132 ML) elk seeds did not result in detectable conversion of the humanised 129 MM PrP substrate, even when similar quantities of PrPres were used to seed the reactions. Low levels of PrPres formation were detected when white tailed deer specimens were tested. The two caribou specimens were both capable of converting the humanised 129 MM PrP substrate efficiently and interestingly, the PRNP codon 129 MV and VV substrates were also readily susceptible to conversion by the caribou seeds.

Conclusions: We previously reported that elk CWD prions were able to convert human PrPC derived from different sources. Here, we expand on this observation analysing more elk specimens of two different genotypes and analysing the conversion potential of white-tailed deer CWD and caribou (reindeer), the latter which have been experimentally infected with white-tailed deer CWD. Our data confirms that CWD prions are able to convert the human PrPC, at least in vitro, and points to caribou and reindeer as a potential source of zoonotic risk.


FRIDAY, JUNE 16, 2017

P55 Susceptibility of human prion protein to in vitro conversion by chronic wasting disease prions

http://chronic-wasting-disease.blogspot ... prion.html

***In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research, however, suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008). It is apparent, though, that CWD is affecting wild and farmed cervid populations in endemic areas with some deer populations decreasing as a result.


https://www.gov.uk/government/uploads/s ... isease.pdf

http://chronic-wasting-disease.blogspot ... ronic.html


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