Tuesday, December 16, 2014

Evidence for zoonotic potential of ovine scrapie prions

Evidence for zoonotic potential of ovine scrapie prions

 

Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014 Article tools Citation Reprints Rights & permissions Article metrics

 

Abstract

 

Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human ​prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

 

Subject terms: Biological sciences• Medical research At a glance

 



see more here ;

http://www.nature.com/ncomms/2014/141216/ncomms6821/extref/ncomms6821-s1.pdf

 

 Scrapie from sheep could infect humans with 'mad cow disease', study finds

 

Tests find a link between the infectious agent behind scrapie with fatal human brain disease, sporadic CJD, which caused major health scare in 1990s

 

A ram being tested for Scrapie

 

A ram being tested for Scrapie Photo: Wayne HUTCHINSON / Alamy

 

By Press Association

 

12:01AM GMT 17 Dec 2014

 

The deadly brain condition known as "mad cow disease" could potentially be transmitted to humans by sheep carrying scrapie, new research suggests.

 

Scientists have concluded that scrapie - the sheep equivalent of mad cow disease, or BSE, in cows - has the potential to infect humans in a similar way to variant CJD (Creuzfeldt Jakob Disease), which caused a major health scare over beef in the 1990s.

 

Tests on mice found a link between the infectious agent behind scrapie with sporadic CJD (sCJD), a fatal human disease whose cause has never been known.

 

The scientists stress they have no proof that eating mutton or lamb infected with scrapie can lead to sCJD in humans.

 

But tests on humanised laboratory mice show that potentially scrapie is capable of infecting humans. And the way the infection spreads in the brain is identical to that seen in cases of sCJD.

 

Related Articles Mad cow infected blood 'to kill 1000’ Mad cow infected blood 'to kill 1,000’ 28 Apr 2013 NHS patients at risk of getting mad cow disease during surgery 24 Jul 2014 Vegetarian diagnosed with 'Mad Cow Disease' 23 Aug 2013

 

The scientists, led by Dr Olivier Andreoletti, from the National Veterinary School of Toulouse in France, wrote in the journal Nature Communications: "Our data on their own do not unequivocally establish a causative link between natural exposure to sheep scrapie and the subsequent appearance of sCJD in humans.

 

"However, our studies clearly point out the need to consider this possibility."

 

Both scrapie and different forms of CJD are caused by rogue misshapen prion proteins. Normal prions that come into contact with the defective versions are changed too and turn "bad". In this way the infection spreads, inflicting terrible damage to the brain.

 

Variant CJD first emerged in 1996 and was shown to be the human version of the cattle disease bovine spongiform encephalopathy (BSE).

 

The prions that caused the disease spread to humans in contaminated beef - especially burgers, cheap cuts and pies - and some cases were also traced to blood transfusions from infected donors.

 

However, fears of a catastrophic epidemic with thousands or even millions of people dying never materialised. To date, 177 UK deaths from vCJD have been recorded, most occurring in the late 1990s and early 2000s.

 

The mice in the new study were the same strain previously used to confirm the ability of BSE to break the species barrier and infect humans.

 

In the tests, the animals had scrapie prions injected straight into their brains. The authors point out that prion infection via non-direct routes, such as eating contaminated tissue, can have an incubation period running into decades.

 

They added: "Furthermore, it is crucial to bear in mind that sporadic sCJD in humans is a rare disease and that scrapie has been circulating in small ruminants populations used for food purposes for centuries.

 

"Consequently, it is our opinion that even if a causative link was established between sheep scrapie exposure and the occurrence of certain sCJD cases, it would be wrong to consider small ruminant (prion) agents as a new major threat for public health."

 

A Defra spokesperson, said: “There are existing measures in place to ensure that any clinically affected animals with this disease are not able to enter the food chain.

 

"Regular surveillance for the disease is carried out in abattoirs and in stock which have died. Scrapie has a very low prevalence within the UK and there are strict biosecurity procedures in place to prevent it entering the country.”

 


 

 

 

Suspect symptoms

 

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

 

28 Mar 01 Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

 

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.

 

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb...

 

2001

 

Suspect symptoms

 

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

 

28 Mar 01

 

Like lambs to the slaughter

 

31 March 2001

 

by Debora MacKenzie Magazine issue 2284.

 

FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

 

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

 

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.

 

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.

 

Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.

 

Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.

 

As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.

 

"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.

 

But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.

 

People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.

 

But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."

 

There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.

 

Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.

 


 

why do we not want to do TSE transmission studies on chimpanzees $

 

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

 

snip...

 

R. BRADLEY

 


 

1: J Infect Dis 1980 Aug;142(2):205-8

 

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

 

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

 

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

 

snip...

 

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

 

PMID: 6997404

 


 

Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"

 

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.

 

snip...

 

76/10.12/4.6

 


 

Nature. 1972 Mar 10;236(5341):73-4.

 

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).

 

Gibbs CJ Jr, Gajdusek DC.

 

Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0

 

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

 

C. J. GIBBS jun. & D. C. GAJDUSEK

 

National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland

 

SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).

 


 


 

Sunday, December 12, 2010

 

EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010

 


 

Wednesday, January 18, 2012

 

Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural Scrapie Isolates Similar to CH1641 Experimental Scrapie

 

Journal of Neuropathology & Experimental Neurology: February 2012 - Volume 71 - Issue 2 - p 140–147

 


 

Thursday, July 14, 2011

 

Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)

 


 

Wednesday, January 18, 2012

 

BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE

 

February 1, 2012

 


 

Thursday, December 23, 2010

 

Molecular Typing of Protease-Resistant Prion Protein in Transmissible Spongiform Encephalopathies of Small Ruminants, France, 2002-2009

 

Volume 17, Number 1 January 2011

 


 

Thursday, November 18, 2010

 

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

 


 

Monday, December 14, 2009

 

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

 

(hmmm, this is getting interesting now...TSS)

 

Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,

 

see also ;

 

All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.

 


 

see full text ;

 

Monday, December 14, 2009

 

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

 


 

Thursday, July 21, 2011

 

A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:

 

August 2011 - Volume 70 - Issue 8 - pp 698-702

 


 

Friday, March 09, 2012

 

Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges

 

Research article

 


 

Thursday, June 23, 2011

 

Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

 


 

Thursday, February 14, 2013

 

*** The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and TSE prion disease

 


 

Tuesday, March 5, 2013

 

Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)

 

FDA believes current regulation protects the public from BSE but reopens comment period due to new studies

 


 

Tuesday, March 05, 2013

 

A closer look at prion strains Characterization and important implications

 

Prion 7:2, 99–108; March/April 2013; © 2013 Landes Bioscience

 


 

Thursday, January 26, 2012

 

Facilitated Cross-Species Transmission of Prions in Extraneural Tissue

 

Science 27 January 2012: Vol. 335 no. 6067 pp. 472-475 DOI: 10.1126/science.1215659

 


 

Saturday, February 11, 2012

 

Prion cross-species transmission efficacy is tissue dependent

 


 

Thursday, January 26, 2012

 

The Risk of Prion Zoonoses

 

Science 27 January 2012: Vol. 335 no. 6067 pp. 411-413 DOI: 10.1126/science.1218167

 


 

Monday, April 25, 2011

 

Experimental Oral Transmission of Atypical Scrapie to Sheep

 

Volume 17, Number 5-May 2011

 


 

Sunday, April 18, 2010

 

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010

 


 

Thursday, November 18, 2010

 

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

 


 

Wednesday, January 19, 2011

 

EFSA and ECDC review scientific evidence on possible links between TSEs in animals and humans Webnachricht 19 Januar 2011

 


 

Monday, June 27, 2011

 

Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease

 


 

Thursday, November 18, 2010

 

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

 


 

Tuesday, September 24, 2013

 

NORDION (US), INC., AND BIOAXONE BIOSCIENCES, INC., Settles $90M Mad Cow TSE prion Contamination Suit Cethrin(R)

 

Case 0:12-cv-60739-RNS Document 1 Entered on FLSD Docket 04/26/2012 Page 1 of 15

 


 

with great sadness and disgust, I must inform you that our federal government has failed us again, and chose the industry over sound science, with regards to TSE prion disease, aka mad cow type disease...tss

 

Saturday, November 2, 2013

 

APHIS Finalizes Bovine Import Regulations in Line with International Animal Health Standards while enhancing the spread of BSE TSE prion mad cow type disease around the Globe

 


 

Wednesday, November 13, 2013

 

Atypical Scrapie Prions from Sheep and Lack of Disease in Transgenic Mice Overexpressing Human Prion Protein

 


 


 

Friday, December 5, 2014

 

SPECIAL ALERT The OIE recommends strengthening animal disease surveillance worldwide

 


 

Tuesday, December 16, 2014

 

Texas 84th Legislature 2015 H.R. No. 2597 Kuempel Deer Breeding Industry TAHC TPWD CWD TSE PRION

 


 

Saturday, December 13, 2014

 

Terry S. Singeltary Sr. Publications TSE prion disease

 

for my files...tss

 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

 

snip...

 


 

Sunday, December 14, 2014

 

ALERT new variant Creutzfeldt Jakob Disease nvCJD or vCJD, sporadic CJD strains, TSE prion aka Mad Cow Disease United States of America Update December 14, 2014 Report

 


 

TSS

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