Saturday, July 6, 2013

Small Ruminant Nor98 Prions Share Biochemical Features with Human Gerstmann-Sträussler-Scheinker Disease and Variably Protease-Sensitive Prionopathy

Research Article
 
 
Small Ruminant Nor98 Prions Share Biochemical Features with Human Gerstmann-Sträussler-Scheinker Disease and Variably Protease-Sensitive Prionopathy
 
 Laura Pirisinu, Romolo Nonno, Elena Esposito, Sylvie L. Benestad, Pierluigi Gambetti, Umberto Agrimi, Wen-Quan Zou
 
 
 
Abstract
 
Prion diseases are classically characterized by the accumulation of pathological prion protein (PrPSc) with the protease resistant C-terminal fragment (PrPres) of 27–30 kDa. However, in both humans and animals, prion diseases with atypical biochemical features, characterized by PK-resistant PrP internal fragments (PrPres) cleaved at both the N and C termini, have been described. In this study we performed a detailed comparison of the biochemical features of PrPSc from atypical prion diseases including human Gerstmann-Sträussler-Scheinker disease (GSS) and variably protease-sensitive prionopathy (VPSPr) and in small ruminant Nor98 or atypical scrapie. The kinetics of PrPres production and its cleavage sites after PK digestion were analyzed, along with the PrPSc conformational stability, using a new method able to characterize both protease-resistant and protease-sensitive PrPSc components. All these PrPSc types shared common and distinctive biochemical features compared to PrPSc from classical prion diseases such as sporadic Creutzfeldt-Jakob disease and scrapie. Notwithstanding, distinct biochemical signatures based on PrPres cleavage sites and PrPSc conformational stability were identified in GSS A117V, GSS F198S, GSS P102L and VPSPr, which allowed their specific identification. Importantly, the biochemical properties of PrPSc from Nor98 and GSS P102L largely overlapped, but were distinct from the other human prions investigated. Finally, our study paves the way towards more refined comparative approaches to the characterization of prions at the animal–human interface.
 
snip...
 
A prion disease with a similar low MW PrPres, Nor98 or atypical scrapie, has been also described in small ruminants [35]. Firstly recognised in Norwegian sheep in 1998 [36], a retrospective study in UK back-dated the presence of Nor98 cases to at least 1989, suggesting that these cases existed in small ruminant populations for years without being detected [37]. Since 2002, Nor98 has been identified in most of EU Member States [35], Canada [38], USA [39] and New Zealand [40]. Unlike classical scrapie, Nor98 occurs with a sporadic distribution [41], [42] and is diagnosed mainly in aged sheep and goats with specific PrP polymorphisms [43], [44]. Although Nor98 is supposed to be a spontaneous disorder [35], [42], [45], it is diagnosed at a relatively high frequency in the EU, with a prevalence of ~4 over 10,000 examined [46]. Despite the lack of epidemiological evidence for natural transmission of Nor98, its transmissibility has been demonstrated in both ovinised transgenic mice [47] and sheep [48], [49], and infectivity was also detected in peripheral tissues [49], [50], indicating that potentially infectious material might enter the food chain.
 
 In this study we aimed at comparing the PrPSc properties of Nor98, GSS and VPSPr cases, getting insight into their apparent similarity and investigating possible relationships among them, particularly at the animal-human interface. To this aim we set up refined biochemical techniques for inter-species comparative epitope mapping of PrPres fragments and for determining the conformational stability of both PK sensitive and PK resistant PrPSc species. Our findings show that GSS, VPSPr and Nor98 share common and distinctive biochemical features, supporting the notion that these atypical forms of PrPSc are not uncommon and characterize a group of prion diseases with different origins (genetic and spontaneous forms) occurring in different hosts. Within this group, we found PrPSc biochemical signatures specific to VPSPr, GSS A117V and GSS F198S, while the phenotypic profile of GSS P102L largely overlapped with that of Nor98.
 
snip...
 
Overall, all Nor98 isolates contained highly PK resistant PrPres aggregates, with the main PrPres being a non-glycosylated internal fragment, cleaved at both the N and C termini, which represent the distinctive biochemical feature of Nor98. This biochemical signature, unique among animal TSEs, is reminiscent of PrPres observed in human prion disorders such as GSS and VPSPr. snip... At present the only epidemiological link between animal and human TSEs has been demonstrated for classical BSE and variant CJD [16], [78], showing for the first time the zoonotic potential of TSEs. Since then, the implementation of active surveillance in livestock has led to the identification of Nor98 and other previously unrecognised animal prion strains, mainly with a sporadic occurrence, whose origin and zoonotic potential are still poorly understood [79]. It has been previously shown that peripheral tissues of sheep with Nor98 might harbour detectable levels of infectivity [49], [50], indicating that infectious material might enter the food chain. On the other hand, the well known genetic aetiology of GSS suggests that the similar PrPSc conformations found in Nor98 and GSS P102L are unlikely to indicate a common infectious source, but might derive from a similar molecular mechanisms involved in PrPC-to-PrPSc conversion. snip...
 
Citation: Pirisinu L, Nonno R, Esposito E, Benestad SL, Gambetti P, et al. (2013) Small Ruminant Nor98 Prions Share Biochemical Features with Human Gerstmann-Sträussler-Scheinker Disease and Variably Protease-Sensitive Prionopathy. PLoS ONE 8(6): e66405. doi:10.1371/journal.pone.0066405
 
Editor: Corinne Ida Lasmezas, The Scripps Research Institute Scripps Florida, United States of America
 
Received: January 24, 2013; Accepted: May 6, 2013; Published: June 24, 2013
 
Copyright: © 2013 Pirisinu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 
Funding: This work was supported by grants from the Italian Ministry of Health (RF-2009-1474624); the European Union (Neuroprion Network of Excellence CT-2004–506579); the National Institutes of Health (NIH) NS062787, NIH AG-08012, AG-14359; Alliance BioSecure, as well as the Center for Disease Control and Prevention Contract UR8/CCU515004. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
 
Competing interests: The authors have declared that no competing interests exist.
 
 
 
 
 
 
 
might...might not....tss
 
 
 
Subject: Food and Rural Affairs on the incidence of transmissible spongiform encephalopathy in the UK sheep flock has been in each of the last 10 years
 
CJD: Sheep
 
Jesse Norman: To ask the Secretary of State for Environment, Food and Rural Affairs what the incidence of transmissible spongiform encephalopathy in the UK sheep flock has been in each of the last 10 years for which data is available. [158834]
 
 
 
Mr Heath [holding answer 12 June 2013]: All cases of transmissible spongiform encephalopathy (TSE) confirmed in the UK sheep flock between 2003 and 2012 have been either classical or atypical scrapie. Cases by year are given in the following table:
 
 
 
 
Classical scrapie Atypical scrapie
 
Total 2003 444 52 496
 
2004 337 16 353
 
2005 229 25 254
 
2006 157 49 206
 
2007 37 36 73
 
2008 9 12 21
 
2009 9 25 34
 
2010 1 19 20
 
2011 49(1) 23 72
 
2012 2 29 31
 
(1) 44 classical scrapie cases in 2011 came from a single flock.
 
 
 
 
 
Greetings,
 
this atypical Nor-98 scrapie, or BSE in sheep ? I don’t know what they mean here, but seems these happenstance of bad luck twisted up proteins i.e. atypical, what some claim to be the old timey, old age TSE, the ones that are _suppose_ to happen spontaneously, if you listen to some officials, seems strange to have 52 cases in 2003, then only 16 cases in 2004, and back up to 49 cases in 2006.
 
 
or it’s not spontaneous at all.
 
 
this is very interesting too ; (1) 44 classical scrapie cases in 2011 came from a single flock. what ever happened to the IBNC BSE in the UK cattle ?
 
 
 
1992
 
NEW BRAIN DISORDER
 
3. WHAT ABOUT REPORTS OF NEW FORM OF BSE ?
 
THE VETERINARY RECORD HAS PUBLISHED AN ARTICLE ON A NEW BRAIN DISORDER OF CATTLE DISCOVERED THROUGH OUR CONTROL MEASURES FOR BSE. ALTHOUGH IT PRESENTS SIMILAR CLINICAL SIGNS TO BSE THERE ARE MAJOR DIFFERENCES IN HISTOPATHOLOGY AND INCUBATION PERIODS BETWEEN THE TWO. MUST EMPHASISE THAT THIS IS _NOT_ BSE.
 
4. IS THIS NEW BRAIN DISORDER A THREAT ?
 
WE DO NOT EVEN KNOW WHETHER THE AGENT OF THIS DISEASE IS TRANSMISSIBLE. IN ANY CASE, CASES SO FAR IDENTIFIED HAD SHOWN SIMILAR SYMPTOMS TO THOSE OF BSE, AND THEREFORE HAVE BEEN SLAUGHTERED AND INCINERATED, SO THAT IF A TRANSMISSIBLE AGENT WERE INVOLVED IT WOULD HAVE BEEN ELIMINATED. ...
 
 
 
 
Tuesday, November 17, 2009
 
SEAC NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC) FROM THE VETERINARY LABORATORIES AGENCY (VLA) SEAC 103/1
 
 
 
 
NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS
 
"All of the 15 cattle tested showed that the brains had abnormally accumulated PrP"
 
2009
 
 
 
 
''THE LINE TO TAKE'' ON IBNC $$$ 1995 $$$
 
1995
 
page 9 of 14 ;
 
30. The Committee noted that the results were unusual. the questioned whether there could be coincidental BSE infection or contamination with scrapie. Dr. Tyrell noted that the feeling of the committee was that this did not represent a new agent but it was important to be prepared to say something publicly about these findings. A suggested line to take was that these were scientifically unpublishable results but in line with the policy of openness they would be made publicly available and further work done to test their validity. Since the BSE precautions were applied to IBNC cases, human health was protected. Further investigations should be carried out on isolations from brains of IBNC cases with removal of the brain and subsequent handling under strict conditions to avoid the risk of any contamination.
 
31. Mr. Bradley informed the Committee that the CVO had informed the CMO about the IBNC results and the transmission from retina and he, like the Committee was satisfied that the controls already in place or proposed were adequate. ...
 
snip... see full text
 
 
 
 
 
Wednesday, July 28, 2010
 
Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA Final report
 
 
 
 
 
IN CONFIDENCE
 
BSE ATYPICAL LESION DISTRIBUTION
 
 
 
 
Tuesday, November 02, 2010
 
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992
 
 
 
 
 
 
Atypical prion protein in sheep brain collected during the British scrapie-surveillance programme
 
S. J. Everest1, L. Thorne1, D. A. Barnicle1, J. C. Edwards1, H. Elliott2, R. Jackman1,† and J. Hope3,†
 
+ Author Affiliations
 
1Department of TSE Molecular Biology, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey KT15 3NB, UK
 
2Institute for Animal Health, Pirbright Laboratory, Woking, Surrey, UK
 
3Veterinary Laboratories Agency Lasswade, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, UK
 
Correspondence J. Hope j.hope@vla.defra.gsi.gov.uk Received 9 March 2005. Accepted 14 October 2005. Abstract Scrapie of sheep and goats is the most common prion disease (or transmissible spongiform encephalopathy, TSE) of mammals and aggregates of abnormal, proteinase-resistant prion protein (PrPSc) are found in all naturally occurring prion diseases. During active surveillance of British sheep for TSEs, 29 201 sheep brain stem samples were collected from abattoirs and analysed for the presence of PrPSc. Of these samples, 54 were found to be positive by using an ELISA screening test, but 28 of these could not be confirmed initially by immunohistochemistry. These unconfirmed or atypical cases were generally found in PrP genotypes normally associated with relative resistance to clinical scrapie and further biochemical analysis revealed that they contained forms of PrPSc with a relatively protease-sensitive amyloid core, some resembling those of Nor98 scrapie. The presence of these atypical forms of protease-resistant PrP raises concerns that some TSE disorders of PrP metabolism previously may have escaped identification in the British sheep population.
 
Previous SectionNext Section ↵†These authors contributed equally to this work.
 
Supplementary material is available in JGV Online.
 
 
 
 
Sunday, August 26, 2012
 
Susceptibility of young sheep to oral infection with bovine spongiform encephalopathy decreases significantly after weaning
 
 
 
 
Wednesday, January 18, 2012
 
BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE
 
February 1, 2012
 
 
 
 
Thursday, April 4, 2013
 
Variably protease-sensitive prionopathy in the UK: a retrospective review 1991–2008
 
Brain (2013) 136 (4): 1102-1115. doi: 10.1093/brain/aws366
 
 
 
 
*** The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
 
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion poker goes up again $
 
OR-10: Variably protease-sensitive prionopathy is transmissible in bank voles
 
Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1 Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome, Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna, Italy; 3Case Western Reserve University; Cleveland, OH USA
 
Background. Variably protease-sensitive prionopathy (VPSPr) is a recently described “sporadic”neurodegenerative disease involving prion protein aggregation, which has clinical similarities with non-Alzheimer dementias, such as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is the electrophoretic pattern of PrPSc after digestion with proteinase K (PK). After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern similar to that described in GSS cases. The clinical and pathological features of VPSPr raised the question of the correct classification of VPSPr among prion diseases or other forms of neurodegenerative disorders. Here we report preliminary data on the transmissibility and pathological features of VPSPr cases in bank voles.
 
Materials and Methods. Seven VPSPr cases were inoculated in two genetic lines of bank voles, carrying either methionine or isoleucine at codon 109 of the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical diagnosis in voles was confirmed by brain pathological assessment and western blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.
 
Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission in BvM109. Overall, 3 voles were positive with survival time between 290 and 588 d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form of the typical PrP27–30, which was indistinguishable to that previously observed in BvM109 inoculated with sCJDMM1 cases.
 
In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until now. Overall, 5 voles were positive with survival time between 281 and 596 d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like PrPSc electrophoretic pattern, characterized by low molecular weight PrPres. These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus and the N-terminus. Second passages are in progress from these first successful transmissions.
 
Conclusions. Preliminary results from transmission studies in bank voles strongly support the notion that VPSPr is a transmissible prion disease. Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.
 
The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
 
 
 
 
 
 
 
 
Monday, January 14, 2013
 
Gambetti et al USA Prion Unit change another highly suspect USA mad cow victim to another fake name i.e. sporadic FFI at age 16 CJD Foundation goes along with this BSe
 
 
 
 
Monday, December 31, 2012
 
Creutzfeldt Jakob Disease and Human TSE Prion Disease in Washington State, 2006–2011-2012
 
 
 
 
Saturday, December 29, 2012
 
MAD COW USA HUMAN TSE PRION DISEASE DECEMBER 29 2012 CJD CASE LAB REPORT
 
 
 
 
MAD COW USDA ATYPICAL L-TYPE BASE BSE, the rest of the story...
 
 
 
 
Tuesday, November 6, 2012
 
Transmission of New Bovine Prion to Mice, Atypical Scrapie, BSE, and Sporadic CJD, November-December 2012 update
 
 
 
 
Tuesday, June 26, 2012
 
Creutzfeldt Jakob Disease Human TSE report update North America, Canada, Mexico, and USDA PRION UNIT as of May 18, 2012
 
type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the rise in Canada and the USA
 
 
 
 
Saturday, March 5, 2011
 
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
 
 
 
 
Sunday, February 12, 2012
 
National Prion Disease Pathology Surveillance Center Cases Examined1 (August 19, 2011) including Texas
 
 
 
 
Monday, August 9, 2010
 
Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more Prionbaloney ?
 
 
 
 
Wednesday, March 28, 2012
 
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion poker goes up again $
 
OR-10 15:25 - 15:40 VARIABLY PROTEASE-SENSITIVE PRIONOPATHY IS TRANSMISSIBLE IN BANK VOLES Nonno
 
 
 
 
Sunday, August 09, 2009
 
CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009
 
 
 
 
Tuesday, August 18, 2009
 
BSE-The Untold Story - joe gibbs and singeltary 1999 – 2009
 
 
 
 
Sunday, February 10, 2013
 
Creutzfeldt-Jakob disease (CJD) biannual update (February 2013) Infection report/CJD
 
 
 
 
Monday, October 10, 2011
 
EFSA Journal 2011 The European Response to BSE: A Success Story
 
snip...
 
EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.
 
snip...
 
 
 
 
 
see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;
 
 
 
 
Thursday, August 12, 2010
 
Seven main threats for the future linked to prions
 
First threat
 
The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.
 
***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.
 
Second threat
 
snip...
 
 
 
 
Saturday, June 25, 2011
 
Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque
 
"BSE-L in North America may have existed for decades"
 
 
 
 
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
 
snip...
 
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
 
 
 
 
Monday, September 26, 2011
 
L-BSE BASE prion and atypical sporadic CJD
 
 
 
 
 
CANADA SEE STEADY INCREASE OF THE SPORADIC CJD’S AND THE VPSPR’S (sporadic CJD’s). ...tss
 
 
PLEASE NOTE, type determination pending Creutzfeldt Jakob Disease (tdpCJD) in Canada is also on a steady increase.
 
please see ;
 
 > 3. Final classification of 50 cases from 2009, 2010, 2011 and 2012 is pending.
 
CJD Deaths Reported by CJDSS1, 1994-20122
 
As of May 31, 2012
 
Deaths of Definite and Probable CJD
 
Year Sporadic Iatrogenic Familial GSS FFI vCJD Total
 
1994 2 0 0 1 0 0 3
 
1995 3 0 0 0 0 0 3
 
1996 13 0 0 0 0 0 13
 
1997 16 0 1 1 0 0 18
 
1998 22 1 0 1 0 0 24
 
1999 26 2 2 1 0 0 31
 
2000 32 0 0 3 0 0 35
 
2001 27 0 2 1 0 0 30
 
2002 31 0 2 2 0 1 36
 
2003 27 1 1 0 0 0 29
 
2004 42 0 1 0 0 0 43
 
2005 42 0 0 2 0 0 44
 
2006 39 0 1 3 1 0 44
 
2007 35 0 0 4 0 0 39
 
2008 48 0 1 0 0 0 49
 
2009 48 0 3 2 0 0 53
 
2010 34 0 3 0 0 0 37
 
2011 37 0 2 1 0 1 41
 
2012 1 0 0 0 0 0 1
 
Total 525 4 19 22 1 2 573
 
1. CJDSS began in 1998
 
2. Data before 1998 are retrospective and partial, data from 1998 to 2008 are complete, and data for 2009 - 2012 are provisional
 
3. Final classification of 50 cases from 2009, 2010, 2011 and 2012 is pending.
 
CJD Deaths Reported by CJDSS1, 1994-20122
 
 
As of May 31, 2012
 
 
 
 
 
 
 
SEE DECEMBER 2012 CANADA
 
 
 
 
 
 
USA SEE STEADY INCREASE OF THE SPORADIC CJD’S AND THE VPSPR’S (sporadic CJD’s). ...tss
 
National Prion Disease Pathology Surveillance Center
 
Cases Examined1
 
(May 18, 2012)
 
Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD
 
1996 & earlier 50 32 28 4 0 0
 
1997 114 68 59 9 0 0
 
1998 88 52 44 7 1 0
 
1999 123 74 65 8 1 0
 
2000 145 103 89 14 0 0
 
2001 210 120 110 10 0 0
 
2002 248 149 125 22 2 0
 
2003 266 168 137 31 0 0
 
2004 326 187 164 22 0 13
 
2005 344 194 157 36 1 0
 
2006 382 196 166 28 0 24
 
2007 377 213 185 28 0 0
 
2008 396 232 206 26 0 0
 
2009 423 256 212 43 1 0
 
2010 413 257 216 41 0 0
 
2011 410 257 213 43 0 0
 
2012 153 82 51 15 0 0
 
TOTAL 44685 26406 2227 387 6 3
 
1 Listed based on the year of death or, if not available, on year of referral;
 
2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted;
 
3 Disease acquired in the United Kingdom;
 
4 Disease was acquired in the United Kingdom in one case and in Saudi Arabia in the other case;
 
5 Includes 14 cases in which the diagnosis is pending, and 18 inconclusive cases;
 
6 Includes 17 (16 from 2012) cases with type determination pending in which the diagnosis of vCJD has been excluded. The Sporadic cases include 16 cases of sporadic Fatal Insomnia (sFI) and 42 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 2118 cases of sporadic Creutzfeldt-Jakob disease (sCJD).
 
 Rev 5/18/2012
 
 
 
 
> 6 Includes
 
 > 17 (16 from 2012) cases with type determination pending in which the diagnosis of vCJD has been excluded.
 
> The Sporadic cases include 16 cases of sporadic Fatal Insomnia (sFI) and 42 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 2118 cases of sporadic Creutzfeldt-Jakob disease (sCJD).
 
 
 
WELL, it seems the USA mad cow strains in humans classified as type determination pending tdpCJD, VPSPr, sFFI, and sCJD) have steadily increased over the years, and the same old song and dance continues with sporadic CJD cases $$$
 
 
 
 
 
 
 
 *** The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
 
Increased Atypical Scrapie Detections
 
Press reports indicate that increased surveillance is catching what otherwise would have been unreported findings of atypical scrapie in sheep. In 2009, five new cases have been reported in Quebec, Ontario, Alberta, and Saskatchewan. With the exception of Quebec, all cases have been diagnosed as being the atypical form found in older animals. Canada encourages producers to join its voluntary surveillance program in order to gain scrapie-free status. The World Animal Health will not classify Canada as scrapie-free until no new cases are reported for seven years. The Canadian Sheep Federation is calling on the government to fund a wider surveillance program in order to establish the level of prevalence prior to setting an eradication date. Besides long-term testing, industry is calling for a compensation program for farmers who report unusual deaths in their flocks.
 
 
 
 
Thursday, March 29, 2012
 
atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012
 
NIAA Annual Conference April 11-14, 2011San Antonio, Texas
 
 
 
 
Monday, April 25, 2011
 
Experimental Oral Transmission of Atypical Scrapie to Sheep
 
Volume 17, Number 5-May 2011 However, work with transgenic mice has demonstrated the potential susceptibility of pigs, with the disturbing finding that the biochemical properties of the resulting PrPSc have changed on transmission (40).
 
 
 
 
 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
 
 
 
 
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
 
 
 
 
P03.141
 
Aspects of the Cerebellar Neuropathology in Nor98
 
Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,
 
Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
 
***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
 
 
 
 
PR-26
 
NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS
 
R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway
 
Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as "atypical" scrapie, as opposed to "classical scrapie". Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion.
 
*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
 
119
 
 
 
 
A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes
 
Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,?? +Author Affiliations
 
*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway
 
***Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)
 
Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. *** These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.
 
 
 
 
Monday, December 1, 2008
 
When Atypical Scrapie cross species barriers
 
Authors
 
Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.
 
Content
 
Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.
 
The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.
 
Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.
 
Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.
 
(i) the unsuspected potential abilities of atypical scrapie to cross species barriers
 
(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier
 
These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.
 
 
 
 
Friday, February 11, 2011
 
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
 
 
 
 
 
RESEARCH
 
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 5, May 2011
 
Experimental Oral Transmission of Atypical Scrapie to Sheep
 
Marion M. Simmons, S. Jo Moore,1 Timm Konold, Lisa Thurston, Linda A. Terry, Leigh Thorne, Richard Lockey, Chris Vickery, Stephen A.C. Hawkins, Melanie J. Chaplin, and John Spiropoulos
 
To investigate the possibility of oral transmission of atypical scrapie in sheep and determine the distribution of infectivity in the animals’ peripheral tissues, we challenged neonatal lambs orally with atypical scrapie; they were then killed at 12 or 24 months. Screening test results were negative for disease-specifi c prion protein in all but 2 recipients; they had positive results for examination of brain, but negative for peripheral tissues. Infectivity of brain, distal ileum, and spleen from all animals was assessed in mouse bioassays; positive results were obtained from tissues that had negative results on screening. These fi ndings demonstrate that atypical scrapie can be transmitted orally and indicate that it has the potential for natural transmission and iatrogenic spread through animal feed. Detection of infectivity in tissues negative by current surveillance methods indicates that diagnostic sensitivity is suboptimal for atypical scrapie, and potentially infectious material may be able to pass into the human food chain.
 
SNIP...
 
Although we do not have epidemiologic evidence that supports the effi cient spread of disease in the fi eld, these data imply that disease is potentially transmissible under fi eld situations and that spread through animal feed may be possible if the current feed restrictions were to be relaxed. Additionally, almost no data are available on the potential for atypical scrapie to transmit to other food animal species, certainly by the oral route. However, work with transgenic mice has demonstrated the potential susceptibility of pigs, with the disturbing fi nding that the biochemical properties of the resulting PrPSc have changed on transmission (40). The implications of this observation for subsequent transmission and host target range are currently unknown.
 
How reassuring is this absence of detectable PrPSc from a public health perspective? The bioassays performed in this study are not titrations, so the infectious load of the positive gut tissues cannot be quantifi ed, although infectivity has been shown unequivocally. No experimental data are currently available on the zoonotic potential of atypical scrapie, either through experimental challenge of humanized mice or any meaningful epidemiologic correlation with human forms of TSE. However, the detection of infectivity in the distal ileum of animals as young as 12 months, in which all the tissues tested were negative for PrPSc by the currently available screening and confi rmatory diagnostic tests, indicates that the diagnostic sensitivity of current surveillance methods is suboptimal for detecting atypical scrapie and that potentially infectious material may be able to pass into the human food chain undetected.
 
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 5, May 2011
 
 
 
 
 Identifying Variation in the U.S. Bovine Prion Gene
 
Bovine spongiform encephalopathy—BSE, or mad cow disease—is a serious threat to the U.S. beef industry.
 
While the first confirmed case of BSE on U.S. soil in December 2003 had little effect on domestic consumption, it carved into our international beef sales. According to USDA’s Economic Research Service, the United States exported only $552 million worth of beef in 2004—down from $2.6 billion in 2002 and $3.1 billion in 2003—a reduction due, in part, to the BSE case.
 
Are some cattle more susceptible to BSE? Is there a genetic component involved?
 
To address these and other questions, ARS scientists at the U.S. Meat Animal Research Center (USMARC) at Clay Center, Nebraska, have sequenced the bovine prion gene, PRNP, in 192 cattle representing 16 beef and 5 dairy breeds common in the United States. This work was partially funded by a grant from USDA’s Cooperative State Research, Education, and Extension Service.
 
Prions are proteins that occur naturally in mammals. BSE is a fatal neurological disorder characterized by irregularly folded prions. Much is unknown about the disease, but scientists recognize a correlation between variations in the PRNP gene in some mammals and susceptibility to transmissible spongiform encephalopathies, such as scrapie in sheep.
 
“Evidence indicates that this could also be true in cattle,” says molecular biologist Mike Clawson. He is among the USMARC scientists examining PRNP variation to learn if and how different forms, or alleles, of the prion gene correlate with BSE susceptibility.
 
A thorough characterization of PRNP variation in a U.S. cattle population will provide a reference framework for researchers to use in analyzing PRNP sequences from cattle afflicted with BSE.
 
From the 192 PRNP genes sequenced, Clawson and his colleagues have identified 388 variations, or polymorphisms, of which 287 were previously unknown. Some of these polymorphisms may influence BSE susceptibility in cattle, he says. Ongoing studies with European collaborators are testing the newly identified variants for association with BSE. If these studies show some cattle to be genetically less susceptible to the disease, this information could shed light on BSE’s transmission and development.
 
The United States has had only three confirmed cases of BSE. Laboratory tests showed that the second and third of these appear to differ significantly from the first case, says Clawson.
 
“By comparing the PRNP sequence from BSE-infected cattle to healthy cattle, we may be able to identify genetic markers in the prion gene that predict BSE susceptibility,” he says.
 
In addition to PRNP, the team is currently sequencing several genes closely related to it. These too will be tested for their association with BSE.
 
“The prevalence of BSE in the United States is extremely low and is declining worldwide,” Clawson says. “Well-characterized genetic markers that correlate to resistance could improve our understanding of the disease and prepare the cattle industry to respond if another prion disease arises in the future.”—By Laura McGinnis, Agricultural Research Service Information Staff.
 
This research is part of Animal Health, an ARS National Program (#103) described on the World Wide Web at www.nps.ars.usda.gov.
 
Michael L. Clawson is at the USDA-ARS Roman L. Hruska U.S. Meat Animal Research Center, P.O. Box 166, Clay Center, NE 68933; phone (402) 762-4342, fax (402) 762-4375.
 
"Identifying Variation in the U.S. Bovine Prion Gene" was published in the January 2007 issue of Agricultural Research magazine.
 
 
 
 
 
Research Project: Susceptibility of Cattle with the E211k Prnp Allele to Bse
 
Location: Virus and Prion Research Unit
 
Project Number: 3625-32000-086-14 Project Type: Specific Cooperative Agreement
 
Start Date: Aug 14, 2008 End Date: Jul 31, 2013
 
Objective:
 
The objective of this cooperative research project is to investigate the influence of the bovine Prnp gene polymorphisms, E211K, on the susceptibility to BSE. Specifically, the research project will provide 134 embryos that will be used to generate approximately 62 animals, 31 of which will contain the rare allele for the purposes BSE research. This ongoing SCA with Iowa State University to produce cattle with the E211K Prnp allele for BSE research has resulted in an E211/K211 heterozygous bull. We are now in the unique position to extend our research on this allele to include animals homozygous for K at position 211. Based upon our understanding of this novel polymorphism one would predict homozygotes would have a more rapid onset of clinical signs associated with genetic BSE than heterozygotes.
 
Approach:
 
To achieve the research goals it is imperative to increase the number of animals available to study this Prnp polymorphism. One female calf of the 2006 BSE case was identified and carries the E211K allele. The specific objectives are to be accomplished through the production of multiple offspring from this E211K heifer through superovulation and embryo transfer. Approximately 50% of the offspring will be heterozygous for the E211K polymorphism while the others will serve as genetically matched non-E211K controls. Collection of semen from an E211K heterozygous bull will allow creation of E211K homozygotes. To protect this unique resource immediate collection of embryos is necessary. The initial goal is to harvest 134 embryos that should result in approximately 62 pregnancies (half of which will carry the E211K polymorphism) for immediate use in the studies to amplify the E211K material, test for genetic susceptibility to TSE, and develop a breeding group to produce calves for transmissibility studies. To achieve the goal of understanding the role of the E211K polymorphism with regard to genetic BSE we have utilized superovulation and embryo transfer obtaining a E211/K211 containing bull. We are now in a position to collect semen from the E211/K211 heterozygous bull to create K211/K211 homozygotes. To accomplish this goal we plan to collect semen from this bull and through artificial insemination using semen from the E211/K211 bull with superovulation and embryo transplantation using other E211/K211 heterzygotes generate 30-40 embryos resulting in 15-20 pregnancies yielding approximately 5 K211/K211 homozygous animals and 10 E211/K211 heterozyous animals as well as 5 E211/E211 homozygous controls.
 
 
 
 
 
Subject: Identifying Variation in the U.S. Bovine Prion Gene Date: January 22, 2007 at 8:32 am PST
 
Identifying Variation in the U.S. Bovine Prion Gene By Laura McGinnis January 22, 2007 Do genes affect bovine spongiform encephalopathy?also known as BSE, or "mad cow" disease? Are some cattle more susceptible than others?
 
To address these and other questions, Agricultural Research Service (ARS) scientists at the U.S. Meat Animal Research Center in Clay Center, Neb., have sequenced the bovine prion gene (PRNP) in 192 cattle that represent 16 beef and five dairy breeds common in the United States.
 
This work, partially funded by a grant from the U.S. Department of Agriculture's Cooperative State Research, Education and Extension Service, is expanding the understanding of how the disease works.
 
BSE is a fatal neurological disorder characterized by prions?proteins that occur naturally in mammals?that fold irregularly. Molecular biologist Mike Clawson and his Clay Center colleagues are examining PRNP variation in order to learn if and how prions correlate with BSE susceptibility.
 
From the 192 PRNP sequences, Clawson and his colleagues have identified 388 variations, or polymorphisms, 287 of which were previously unknown. Some of these polymorphisms may influence BSE susceptibility in cattle.
 
Comparing PRNP sequences from infected and healthy cattle may enable researchers to identify genetic markers in the prion gene that predict BSE susceptibility. In addition to PRNP, the team is currently sequencing several closely related genes, which will also be tested for their association with BSE.
 
The prevalence of BSE in the United States is extremely low, but this research could improve understanding of the disease and prepare the cattle industry to respond if another prion disease should arise in the future.
 
 
 
 
Identifying Variation in the U.S. Bovine Prion Gene
 
Bovine spongiform encephalopathy (BSE, or mad cow disease) is a serious threat to the U.S. beef industry.
 
While the first confirmed case of BSE on U.S. soil in December 2003 had little effect on domestic consumption, it carved into our international beef sales. According to USDAs Economic Research Service, the United States exported only $552 million worth of beef in 2004 down from $2.6 billion in 2002 and $3.1 billion in 2003 a reduction due, in part, to the BSE case.
 
Are some cattle more susceptible to BSE? Is there a genetic component involved?
 
To address these and other questions, ARS scientists at the U.S. Meat Animal Research Center (USMARC) at Clay Center, Nebraska, have sequenced the bovine prion gene, PRNP, in 192 cattle representing 16 beef and 5 dairy breeds common in the United States. This work was partially funded by a grant from USDA?s Cooperative State Research, Education, and Extension Service.
 
Prions are proteins that occur naturally in mammals. BSE is a fatal neurological disorder characterized by irregularly folded prions. Much is unknown about the disease, but scientists recognize a correlation between variations in the PRNP gene in some mammals and susceptibility to transmissible spongiform encephalopathies, such as scrapie in sheep.
 
Evidence indicates that this could also be true in cattle, says molecular biologist Mike Clawson. He is among the USMARC scientists examining PRNP variation to learn if and how different forms, or alleles, of the prion gene correlate with BSE susceptibility.
 
A thorough characterization of PRNP variation in a U.S. cattle population will provide a reference framework for researchers to use in analyzing PRNP sequences from cattle afflicted with BSE.
 
From the 192 PRNP genes sequenced, Clawson and his colleagues have identified 388 variations, or polymorphisms, of which 287 were previously unknown. Some of these polymorphisms may influence BSE susceptibility in cattle, he says. Ongoing studies with European collaborators are testing the newly identified variants for association with BSE. If these studies show some cattle to be genetically less susceptible to the disease, this information could shed light on BSEs transmission and development.
 
The United States has had only three confirmed cases of BSE. Laboratory tests showed that the second and third of these appear to differ significantly from the first case, says Clawson.
 
By comparing the PRNP sequence from BSE-infected cattle to healthy cattle, we may be able to identify genetic markers in the prion gene that predict BSE susceptibility, he says.
 
In addition to PRNP, the team is currently sequencing several genes closely related to it. These too will be tested for their association with BSE.
 
The prevalence of BSE in the United States is extremely low and is declining worldwide, Clawson says. Well-characterized genetic markers that correlate to resistance could improve our understanding of the disease and prepare the cattle industry to respond if another prion disease arises in the future. By Laura McGinnis, Agricultural Research Service Information Staff.
 
This research is part of Animal Health, an ARS National Program (#103) described on the World Wide Web at www.nps.ars.usda.gov.
 
Michael L. Clawson is at the USDA-ARS Roman L. Hruska U.S. Meat Animal Research Center, P.O. Box 166, Clay Center, NE 68933; phone (402) 762-4342, fax (402) 762-4375.
 
 
 
 
 
Title: Prion gene haplotypes of U.S. cattle
 
Authors
 
Clawson, Michael - mike Heaton, Michael - mike Keele, John Smith, Timothy - tim Harhay, Gregory Laegreid, William - will
 
Submitted to: BioMed Central (BMC) Genetics Publication Type: Peer Reviewed Journal Publication Acceptance Date: October 24, 2006 Publication Date: November 8, 2006 Reprint URL: http://www.biomedcentral.com/1471-2156/7/51 Citation: Clawson, M.L., Heaton, M.P., Keele, J.W., Smith, T.P., Harhay, G.P., Laegreid, W.W. 2006. Prion gene haplotypes of U.S. cattle. BioMed Central (BMC) Genetics. 7:51.
 
Interpretive Summary: Transmissible spongiform encephalopathies (TSEs) are fatal neurological disorders that are characterized by abnormal deposits of the prion protein. TSEs have been identified in cats, cattle, deer, elk, humans, mink, moose, and sheep. The cattle TSE, bovine spongiform encephalopathy (BSE) is also known as mad cow disease. BSE is the probable cause of the human TSE variant Creutzfeldt-Jakob disease, transmitted from cattle to people via the food chain. Sequence variation in the prion gene correlates with TSE progression in humans, sheep, and mice. Additionally, there is evidence that bovine PRNP variation correlates with BSE progression. In this study, 25.2 kb of PRNP was sequenced from the promoter region through the three prime untranslated region in 192 U.S. cattle (16 beef, five dairy breeds). Three hundred and eighty eight polymorphisms were observed, of which 287 have not been previously reported. A subset of polymorphisms that efficiently tag genetic variation in U.S. cattle was identified. The results of this study provide a reference framework for accurate and comprehensive evaluation of prion gene variation and its relationship to BSE. Technical Abstract: Background: Bovine spongiform encephalopathy (BSE) is a fatal neurological disorder characterized by abnormal deposits of a protease-resistant isoform of the prion protein. Characterizing linkage disequilibrium (LD) and haplotype networks within the bovine prion gene (PRNP) is important for 1) testing rare or common PRNP variation for an association with BSE and 2) interpreting any association of PRNP alleles with BSE susceptibility. The objective of this study was to identify polymorphisms and haplotypes within PRNP from the promoter region through the 3'UTR in a diverse sample of U.S. cattle genomes. Results: A 25.2-kb genomic region containing PRNP was sequenced from 192 diverse U.S. beef and dairy cattle. Sequence analyses identified 388 total polymorphisms, of which 287 have not previously been reported. The polymorphism alleles define PRNP by regions of high and low LD. High LD is present between alleles in the promoter region through exon 2 (6.7 kb). PRNP alleles within the majority of intron 2, the entire coding sequence and the untranslated region of exon 3 are in low LD (18.0 kb). Two haplotype networks, one representing the region of high LD and the other the region of low LD yielded nineteen different combinations that represent haplotypes spanning PRNP. The haplotype combinations are tagged by 19 polymorphisms (htSNPS) which characterize variation within and across PRNP.
 
Conclusion: The number of polymorphisms in the prion gene region of U.S. cattle is nearly four times greater than previously described. These polymorphisms define PRNP haplotypes that may influence BSE susceptibility in cattle.
 
 
 
 
Title: Frequencies of polymorphisms associated with BSE resistance differ significantly between Bos taurus, Bos indicus, and composite cattle
 
Authors
 
BRUNELLE, BRIAN GREENLEE, JUSTIN Seabury, Christopher - TEXAS A&M UNIVERSITY Brown Ii, Charles - ABS GLOBAL NICHOLSON, ERIC
 
Submitted to: BioMed Central (BMC) Veterinary Research Publication Type: Peer Reviewed Journal Publication Acceptance Date: August 22, 2008 Publication Date: August 22, 2008 Citation: Brunelle, B.W., Greenlee, J.J., Seabury, C.M., Brown II, C.E., Nicholson, E.M. 2008. Frequencies of Polymorphisms Associated with BSE Resistance Differ Significantly Between Bos taurus, Bos indicus, and Composite Cattle. BioMed Central (BMC) Veterinary Research. 4(1):36. Available: http://www.biomedcentral.com/1746-6148/4/36.
 
Interpretive Summary: Bovine spongiform encephalopathy (BSE) is a neurodegenerative prion disease of cattle. There are three host factors related to the host prion protein known to influence susceptibility or resistance to BSE: single amino acid changes in the prion protein, repeat regions within the prion protein, and expression levels of the prion protein. These factors have been well documented in breeds of Bos taurus cattle, but there is little-to-no data on these factors in Bos indicus purebred or Bos indicus x Bos taurus crossbred cattle. Since Bos indicus cattle contribute to the U.S. cattle population, we wanted to determine the frequency of the host factors associated with BSE susceptibility. We studied 58 Bos indicus purebred and 38 Bos indicus x Bos taurus crossbred cattle. The only differences between Bos indicus and Bos taurus cattle were in two factors associated with prion protein expression levels. It was observed that Bos indicus cattle had a much higher frequency of one factor associated with resistance to BSE compared to Bos taurus cattle, while the second factor associated with resistance to BSE was much lower in Bos indicus cattle compared to Bos taurus cattle. This data is useful in determining the relative risk of BSE in Bos indicus cattle based upon these factors. Technical Abstract: Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that affect several mammalian species. At least three factors related to the host prion protein are known to modulate susceptibility or resistance to a TSE: amino acid sequence, atypical number of octapeptide repeats, and expression level. These factors have been extensively studied in breeds of Bos taurus cattle in relation to bovine spongiform encephalopathy (BSE). However, little is currently known about these factors in Bos indicus purebred or B. indicus x B. taurus crossbred cattle. The goal of our study was to establish the frequency of markers associated with enhanced susceptibility or resistance to BSE in B. indicus purebred and crossbred cattle.
 
 
 
 
18 January 2007 - Draft minutes of the SEAC 95 meeting (426 KB) held on 7 December 2006 are now available.
 
snip...
 
ITEM 9 - ANY OTHER BUSINESS
 
snip...
 
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
 
64. A member noted that at the recent Neuroprion meeting, a study was presented showing that in transgenic mice BSE passaged in sheep may be more virulent and infectious to a wider range of species than bovine derived BSE. Other work presented suggested that BSE and bovine amyloidotic spongiform encephalopathy (BASE) MAY BE RELATED. A mutation had been identified in the prion protein gene in an AMERICAN BASE CASE THAT WAS SIMILAR IN NATURE TO A MUTATION FOUND IN CASES OF SPORADIC CJD. A study also demonstrated that in a mouse model it was possible to alleviate the pathological changes of prion disease by suppressing expression of the prion protein gene after infection.
 
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
 
NOW PLEASE GO BACK AND READ THAT SECOND PARAGRAPH AGAIN.....TSS
 
 
 
PLEASE READ FULL TEXT ;
 
 
 
 
Discussion
 
This study assessed the prevalence of specific BSE-associated factors in B. indicus purebred and composite cattle, which were then compared to frequencies observed in B. taurus cattle. Through PRNP sequence analysis, we surveyed cattle for the presence of an E211K amino acid replacement, as well as the presence of 7 or more octapeptide repeats. In addition, we determined the frequencies of the 23-bp and 12-bp indel regions associated with bovine PRNP transcriptional regulation.
 
None of the PRNP alleles for the B. indicus samples evaluated in this study exhibited an E211K amino acid replacement or any novel coding region polymorphism. To date, the E211K change has been reported in only two bovine samples, the 2006 Alabama atypical BSE case [7] and its only known living offspring [8]. The affected animal was a composite (B. taurus × B. indicus), but because no parental information is currently available, it is unknown whether the corresponding nucleotide change was inherited or the result of spontaneous mutation. If it was inherited, then the E211K allele may have originated in either a B. taurus ancestor or a B. indicus ancestor. Unfortunately, the data presented here cannot facilitate a species level assignment, as the PRNP coding sequence of the 2006 Alabama case did not possess any species-specific polymorphisms. This particular animal was determined to possess one haplotype with a 23 and 12-bp insertion, and the other with a 23 and 12-bp deletion [27]. These 2 haplotypes occur in 92% of B. taurus, but only in 25% B. indicus cattle (Table ?(Table1),1), as estimated by our analyses. Unless more information becomes available, it cannot be determined where the E211K replacement may have originated.
 
No B. indicus sample had an octapeptide region containing more than 6 repeats. Notably, humans are the only TSE-susceptible mammal besides the Brown Swiss breed of B. taurus cattle for which additional octapeptide repeats have been observed. Interestingly, a transgenic mouse model expressing bovine PrPC with 1 extra repeat was more susceptible to BSE challenge than a transgenic mouse with the normal number of repeats, but did not develop a spontaneous prion disease [14]. However, a transgenic mouse expressing a bovine PRNP gene encoding 4 additional repeats did in fact develop a spontaneous prion disease [15]. While cattle with 1 additional octapeptide repeat may have an enhanced risk for classical BSE only if exposed to infected material, the appearance of PRNP genes encoding extra octapeptide repeats in any cattle breed may be cause for concern.
 
The incidence of E211K as well as octapeptide regions with 7 repeats among cattle does not provide a species-level explanation for potential differences in susceptibility to BSE among B. taurus and B. indicus cattle. Therefore, only the 23-bp and 12-bp indel regions seem pertinent in these populations because both of these bovine PRNP sequence regions have been shown to influence transcription levels of PrPC. The B. indicus purebred and composite cattle had a very low frequency of the 23-bp insertion as compared to B. taurus, while only B. indicus purebred cattle had a high frequency of the 12-bp insertion. To date, no consensus has emerged regarding whether one of these bovine PRNP regions is more influential than the other with respect to classical BSE resistance in cattle. Originally, only the 23-bp region was found to be significantly associated with (classical) BSE resistance [26]. Using a reporter gene assay, it was later concluded that the 23-bp indel region was the most relevant locus, as the only constructs that lowered expression levels were those containing the 23-bp insertion [25]. In contrast, other reports indicate the 12-bp indel is more relevant both statistically [24] and in a reporter gene assay [30]. The discrepancy between the significance of these two regions with respect to resistance or susceptibility to classical BSE may be influenced by 3 or more factors. First, the 23-bp and 12-bp regions are physically linked (~2-Kbp apart). Therefore, recombination is most likely rare given the small distance separating the two indel polymorphisms. Moreover, high levels of linkage disequilibrium have been detected for genetic variation within the bovine PRNP promoter and intron 1 [31]. Secondarily, the 23-bp insertion and 12-bp deletion haplotype is absent among cattle surveyed to date, thereby creating an equal-to-greater overall frequency of 12-bp insertions as compared to the frequency spectrum of 23-bp insertions. More specifically, twice as many haplotypes (n = 12) contribute to the overall frequency of the 12-bp intron 1 insertion as those contributing to the frequency of the 23-bp insertion (n = 6; Table ?Table2).2). This may inevitably bias indel association studies. Lastly, species specific allelic variation associated with the genetic backgrounds of B. taurus and B. indicus may differentially interact with the 23-bp promoter and 12-bp intron 1 PRNP polymorphisms, perhaps making each polymorphism more or less relevant in a particular bovine species. On the basis of indel genotype alone, if it is ultimately concluded that the 23-bp insertion has a greater influence than the 12-bp insertion with respect to resistance to classical BSE in cattle following exposure to infected material, B. indicus purebred and composite cattle would be at greater risk than B. taurus cattle. Conversely, if the 12-bp insertion were to modulate a greater level of resistance to BSE, then B. indicus cattle would be at a lower risk than B. taurus and composite cattle.
 
Other Sections?
 
Conclusion
 
We determined the frequencies of known genetic factors associated with differential susceptibility to BSE in B. indicus purebred and B. indicus × B. taurus composite cattle, as compared to B. taurus purebred cattle. No deviations from the expected numbers of octapeptide repeats were detected for B. indicus purebred and composite cattle. Likewise, the E211K substitution was not detected within the PRNP coding sequences for cattle investigated herein. However, a significant difference was detected for a comparison of the 23-bp and 12-bp indel genotype frequencies between B. indicus and B. taurus cattle. The origin of this result could be attributed to significant differences in haplotype frequencies among B. indicus, B. taurus, and composite cattle. Currently, it is unknown which bovine PRNP region (23-bp promoter; 12-bp intron 1), if either, may be more important with respect to differential susceptibility to classical BSE in cattle following exposure to the etiologic agent. Should either the 23-bp promoter region or the 12-bp intron 1 region of the bovine PRNP prove more biologically relevant to the manifestation of disease, substantial heritable differences in overall susceptibility or resistance to classical BSE may exist between B. indicus and B. taurus cattle.
 
 
 
 
let's take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.
 
This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$
 
ALABAMA MAD COW g-h-BSEalabama
 
In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.
 
 
 
 
 
her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008).
 
This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine–human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks.
 
Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA
 
NATURE|Vol 457|26 February 2009
 
 
 
 
Saturday, August 14, 2010
 
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY
 
(see mad cow feed in COMMERCE IN ALABAMA...TSS)
 
 
 
 
 
 
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).
 
 
 
 
 
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. Subscribe and get 4 free issues. 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.
 
 
 
 
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
 
 
 
 
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
 
 
 
 
 
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
 
 
 
 
Thursday, November 18, 2010
 
Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep
 
 
 
 
Monday, November 30, 2009
 
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE
 
 
 
 
Thursday, December 20, 2012
 
OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED AND SAME OLD BSe WITH BOVINE MAD COW DISEASE
 
 
 
 
Thursday, May 30, 2013
 
World Organization for Animal Health (OIE) has upgraded the United States' risk classification for mad cow disease to "negligible" from "controlled", and risk further exposing the globe to the TSE prion mad cow type disease
 
U.S. gets top mad-cow rating from international group and risk further exposing the globe to the TSE prion mad cow type disease
 
 
 
 
 
 
 
Monday, June 3, 2013
 
Unsuccessful oral transmission of scrapie from British sheep to cattle
 
 
 
 
 
 
 
DEEP THROAT TO TSS 2000-2001 (take these old snips of emails with how ever many grains of salt you wish. ...tss)
 
 
The most frightening thing I have read all day is the report of Gambetti's finding of a new strain of sporadic cjd in young people...Dear God, what in the name of all that is holy is that!!! If the US has different strains of scrapie.....why???? than the UK...then would the same mechanisms that make different strains of scrapie here make different strains of BSE...if the patterns are different in sheep and mice for scrapie.....could not the BSE be different in the cattle, in the mink, in the humans.......I really think the slides or tissues and everything from these young people with the new strain of sporadic cjd should be put up to be analyzed by many, many experts in cjd........bse.....scrapie Scrape the damn slide and put it into mice.....wait.....chop up the mouse brain and and spinal cord........put into some more mice.....dammit amplify the thing and start the damned research.....This is NOT rocket science...we need to use what we know and get off our butts and move....the whining about how long everything takes.....well it takes a whole lot longer if you whine for a year and then start the research!!!
 
 
Not sure where I read this but it was a recent press release or something like that: I thought I would fall out of my chair when I read about how there was no worry about infectivity from a histopath slide or tissues because they are preserved in formic acid, or formalin or formaldehyde.....for God's sake........ Ask any pathologist in the UK what the brain tissues in the formalin looks like after a year.......it is a big fat sponge...the agent continues to eat the brain ......you can't make slides anymore because the agent has never stopped........and the old slides that are stained with Hemolysin and Eosin......they get holier and holier and degenerate and continue...what you looked at 6 months ago is not there........Gambetti better be photographing every damned thing he is looking at.....
 
 
Okay, you need to know. You don't need to pass it on as nothing will come of it and there is not a damned thing anyone can do about it. Don't even hint at it as it will be denied and laughed at.......... USDA is gonna do as little as possible until there is actually a human case in the USA of the nvcjd........if you want to move this thing along and shake the earth....then we gotta get the victims families to make sure whoever is doing the autopsy is credible, trustworthy, and a saint with the courage of Joan of Arc........I am not kidding!!!! so, unless we get a human death from EXACTLY the same form with EXACTLY the same histopath lesions as seen in the UK nvcjd........forget any action........it is ALL gonna be sporadic!!!
 
 
And, if there is a case.......there is gonna be every effort to link it to international travel, international food, etc. etc. etc. etc. etc. They will go so far as to find out if a sex partner had ever traveled to the UK/europe, etc. etc. .... It is gonna be a long, lonely, dangerous twisted journey to the truth. They have all the cards, all the money, and are willing to threaten and carry out those threats....and this may be their biggest downfall...
 
 
Thanks as always for your help. (Recently had a very startling revelation from a rather senior person in government here..........knocked me out of my chair........you must keep pushing. If I was a power person....I would be demanding that there be a least a million bovine tested as soon as possible and agressively seeking this disease. The big players are coming out of the woodwork as there is money to be made!!! In short: "FIRE AT WILL"!!! for the very dumb....who's "will"! "Will be the burden to bare if there is any coverup!"
 
 
again it was said years ago and it should be taken seriously....BSE will NEVER be found in the US! As for the BSE conference call...I think you did a great service to freedom of information and making some people feign integrity...I find it scary to see that most of the "experts" are employed by the federal government or are supported on the "teat" of federal funds. A scary picture! I hope there is a confidential panel organized by the new government to really investigate this thing.
 
 
You need to watch your back........but keep picking at them.......like a buzzard to the bone...you just may get to the truth!!! (You probably have more support than you know. Too many people are afraid to show you or let anyone else know. I have heard a few things myself... you ask the questions that everyone else is too afraid to ask.)
 
 
END...
 
 
 
 
$$$

Monday, June 11, 2012

another atypical Nor-98 Scrapie case documented in Canada for 2012

another atypical Nor-98 Scrapie case documented in Canada for 2012


Date confirmed Location Animal type infected May 31* Quebec Sheep






Sunday, April 29, 2012


Scrapie confirmed at quarantined sheep farm Canada CFIA





Wednesday, April 4, 2012


20120402 - Breach of quarantine/Violation de la mise en quarantaine of an ongoing Scrapie investigation





Thursday, February 23, 2012


Atypical Scrapie NOR-98 confirmed Alberta Canada sheep January 2012





Thursday, March 29, 2012


atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012


NIAA Annual Conference April 11-14, 2011San Antonio, Texas





Monday, November 30, 2009


USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE





Friday, June 8, 2012


Canadian Food Inspection Agency locates missing sheep





Sunday, May 27, 2012


CANADA PLANS TO IMPRISON ANYONE SPEAKING ABOUT MAD COW or ANY OTHER DISEASE OUTBREAK, CENSORSHIP IS A TERRIBLE THING






TSS
 

Thursday, March 29, 2012

atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012

NIAA Annual Conference April 11-14, 2011San Antonio, Texas




Nor98-Like Scrapie Cases in the United States

Total number of cases since first detected in 2007

•12

Mean age of infected animals

•6 Years

Median age of infected animals

•5 years

Sex Distribution of infected animals

•12 females

Face Color Distribution of infected animals

•8 White or Minimally Mottled

•2 Mottled

•1 Black

•1 SoayClinical signs

•1 animal




Nor98-Like Scrapie Cases in the United States

Genotypes

•3 AFRQ/ALRQ

•2 AFRQ/AFRQ

•2 ALHQ/ALRQ

•2 ALRR/ALRR

•1 ALRQ/ALRQ

•1 ALHQ/ALHQ

•1 AFRQ/ALRRAllele


frequency


•8 AFRQ

•7 ALRQ

•5 ALRR

•4 ALHQ






RSSS InvestigationsFY 2011*

•6 classical scrapie positives detected.

•6 successfully traced back to flock of origin, resulting in 6 newly discovered Infected or Source flocks.

•No investigations pending.

* As of February 28, 2011




Scrapie Confirmed Cases inFY 2010


Classical scrapie cases = 72;

Nor98-like scrapie cases = 5


53 Field Cases;

24 RSSS cases (n) (Reported by State of ID tag). Each asterisk *indicates one Nor98-like case. Note: field cases include animals removed from infected/source flocks so the state totals often include several animals from the same flock.




Scrapie Confirmed Cases in FY 2011 as of February 28, 2011


Classical scrapie cases = 11; Nor98-like scrapie cases = 1

6 Field Cases;

6 RSSS cases (n) (Reported by State of ID tag). Each asterisk *indicates one Nor98-like case. Note: field cases include animals removed from infected/source flocks so the state totals often include several animals from the same flock.



Goat Scrapie Cases FY 2002 –FY 2011*


Total Goat Cases = 22


* Through February 28, 2011


http://www.animalagriculture.org/Solutions/Proceedings/Annual%20Conference/2011/Small%20Ruminant/Garrett,%20Joe.pdf




Monday, October 10, 2011

EFSA Journal 2011 The European Response to BSE: A Success Story

snip...

EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.

snip...


http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1



http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf




see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html



Monday, November 30, 2009

USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE

http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html




Friday, February 11, 2011

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

http://nor-98.blogspot.com/2011/02/atypicalnor98-scrapie-infectivity-in.html




Sunday, December 12, 2010

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

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/efsa-reviews-bsetse-infectivity-in.html




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

http://transmissiblespongiformencephalopathy.blogspot.com/2012/01/selection-of-distinct-strain-phenotypes.html



Thursday, July 14, 2011

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

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/histopathological-studies-of-ch1641.html




Wednesday, January 18, 2012

BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE

February 1, 2012

http://transmissiblespongiformencephalopathy.blogspot.com/2012/01/bse-in-goats-can-be-mistaken-for.html



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

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/molecular-typing-of-protease-resistant.html



Thursday, November 18, 2010

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

http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html






P03.141

Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,

Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf





PR-26

NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS

R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway

Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as "atypical" scrapie, as opposed to "classical scrapie". Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion.

*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.

119

http://www.neuroprion.com/pdf_docs/conferences/prion2006/abstract_book.pdf





A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,? +Author Affiliations

*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway

***Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)

Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. *** These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.

http://www.pnas.org/content/102/44/16031.abstract





Monday, December 1, 2008

When Atypical Scrapie cross species barriers

Authors

Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.

Content

Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.

The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.

Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.

Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.

(i) the unsuspected potential abilities of atypical scrapie to cross species barriers

(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier

These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.

http://www.neuroprion.org/resources/pdf_docs/conferences/prion2008/abstract-book-prion2008.pdf




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

http://transmissiblespongiformencephalopathy.blogspot.com/2012/01/facilitated-cross-species-transmission.html




Saturday, February 11, 2012

Prion cross-species transmission efficacy is tissue dependent

http://transmissiblespongiformencephalopathy.blogspot.com/2012/02/prion-cross-species-transmission.html




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

http://transmissiblespongiformencephalopathy.blogspot.com/2012/01/risk-of-prion-zoonoses.html




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

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract




12/10/76

AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE

Office Note CHAIRMAN: PROFESSOR PETER WILDY

snip...

A The Present Position with respect to Scrapie A] The Problem Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries. The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep. It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible. 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

http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf




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).

http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html




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).

http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html




Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE

http://scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.html




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


snip...

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

http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf




Friday, February 11, 2011

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

http://nor-98.blogspot.com/2011/02/atypicalnor98-scrapie-infectivity-in.html




Monday, April 25, 2011

Experimental Oral Transmission of Atypical Scrapie to Sheep

Volume 17, Number 5-May 2011

http://nor-98.blogspot.com/2011/04/experimental-oral-transmission-of.html




Sunday, April 18, 2010

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010

http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html




Thursday, November 18, 2010

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

http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html




Wednesday, January 19, 2011

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

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/efsa-and-ecdc-review-scientific.html




Monday, June 27, 2011

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

http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html





RESEARCH

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 5, May 2011

Experimental Oral Transmission of Atypical Scrapie to Sheep

Marion M. Simmons, S. Jo Moore,1 Timm Konold, Lisa Thurston, Linda A. Terry, Leigh Thorne, Richard Lockey, Chris Vickery, Stephen A.C. Hawkins, Melanie J. Chaplin, and John Spiropoulos

To investigate the possibility of oral transmission of atypical scrapie in sheep and determine the distribution of infectivity in the animals’ peripheral tissues, we challenged neonatal lambs orally with atypical scrapie; they were then killed at 12 or 24 months. Screening test results were negative for disease-specifi c prion protein in all but 2 recipients; they had positive results for examination of brain, but negative for peripheral tissues. Infectivity of brain, distal ileum, and spleen from all animals was assessed in mouse bioassays; positive results were obtained from tissues that had negative results on screening. These fi ndings demonstrate that atypical scrapie can be transmitted orally and indicate that it has the potential for natural transmission and iatrogenic spread through animal feed. Detection of infectivity in tissues negative by current surveillance methods indicates that diagnostic sensitivity is suboptimal for atypical scrapie, and potentially infectious material may be able to pass into the human food chain.

SNIP...

Although we do not have epidemiologic evidence that supports the effi cient spread of disease in the fi eld, these data imply that disease is potentially transmissible under fi eld situations and that spread through animal feed may be possible if the current feed restrictions were to be relaxed. Additionally, almost no data are available on the potential for atypical scrapie to transmit to other food animal species, certainly by the oral route. However, work with transgenic mice has demonstrated the potential susceptibility of pigs, with the disturbing fi nding that the biochemical properties of the resulting PrPSc have changed on transmission (40). The implications of this observation for subsequent transmission and host target range are currently unknown.

How reassuring is this absence of detectable PrPSc from a public health perspective? The bioassays performed in this study are not titrations, so the infectious load of the positive gut tissues cannot be quantifi ed, although infectivity has been shown unequivocally. No experimental data are currently available on the zoonotic potential of atypical scrapie, either through experimental challenge of humanized mice or any meaningful epidemiologic correlation with human forms of TSE. However, the detection of infectivity in the distal ileum of animals as young as 12 months, in which all the tissues tested were negative for PrPSc by the currently available screening and confi rmatory diagnostic tests, indicates that the diagnostic sensitivity of current surveillance methods is suboptimal for detecting atypical scrapie and that potentially infectious material may be able to pass into the human food chain undetected.

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 5, May 2011

http://wwwnc.cdc.gov/eid/article/17/5/pdfs/10-1654.pdf




OIE Scrapie Chapter Revision • Current draft recognizes Nor98-like scrapie as a separate disease from classical scrapie • USDA provided comments on the draft to OIE

http://www.animalagriculture.org/Solutions/Proceedings/Annual%20Meeting/2009/Sheep%20&%20Goat/Myers,%20Thomas.pdf




Atypical scrapie/Nor 98 October 2009

Last year, after examining member country submissions and investigating rigorous scientific research, the World Organisation for Animal Health (OIE) decided that Nor 98 should not be listed in its Terrestrial Animal Health Code. The Code sets out trade recommendations or restrictions for listed diseases or conditions, and the OIE determined there was no need for such recommendations around Nor 98.


http://www.nzfsa.govt.nz/publications/ce-column/ce-web-nor98.htm




http://www.biosecurity.govt.nz/files/pests/atypical-scrapie/atypical-scrapie-faq-oct09.pdf




Sutton reported that USDA has urged the World Organization for Animal Health (OIE) to categorize Nor98-like scrapie as a separate disease from classical scrapie. Currently, the OIE has proposed a draft revision of their scrapie chapter that would exclude Nor98-like scrapie from the chapter. USDA will be submitting it's comments on this proposal soon.

http://www.ohiosheep.org/Events/ScrapieNewsletterMarch09.pdf




SCRAPIE

The United States is unable to support the proposed new draft Code Chapter on Scrapie. The draft chapter, as written, departs significantly from the existing chapter, is confusing and is difficult to understand. This version of the scrapie chapter uses much of the same wording as the BSE chapter and is written as if the predominance of evidence revealed that scrapie was a food-borne disease similar to BSE in cattle which is inappropriate. Moreover, several of the new changes are not supported by current scientific evidence. As a result, detailed comments on individual articles would not meaningful at this time.

The United States is not supportive of the proposed draft chapter for the following reasons: 1. Inclusion of “atypical” scrapie: The scientific evidence indicates that “atypical” scrapie, also referred to as Nor-98, Nor-98-like, or non-classical scrapie, is not the same disease as classical scrapie. Further, “atypical” scrapie does not meet the criteria for listing diseases of trade concern by the OIE, as described in Chapter 2.1.1 of the Code. The United States recommends that the scope of this chapter be limited to classical scrapie in sheep and goats. Further, the United States recommends that OIE clearly adopt the position that “atypical” scrapie represents a distinct disease entity from classical scrapie and that it not be a listed disease.

• There is no evidence that “atypical” scrapie is a contagious disease. If it is contagious, available evidence suggests that it has a much lower transmission efficiency. (Hopp, et al, 2006; Green, et al, 2007; Benestad, et al 2008; McIntyre, et al, 2008)

• The disease appears to be ubiquitous in that it has been found wherever sufficient surveillance has been conducted. (Buschmann et al, 2004; De Bosschere et al, 2004; Orge, et al, 2004; Everest et al, 2006; Arsac, 2007; Benestad, et al 2008; Fediaevsky, et al, 2008)

• The disease does not appear to be economically significant in that the prevalence of clinical disease is low and it typically occurs in older animals. (Luhken, et al., 2007; Benestad, et al 2008).

• The disease is as likely as not to be the result of a spontaneous conversion of normal prion protein. (Benestad, et al 2008, De Bosschere et al 2007)

• Removal of exposed sheep is unlikely to reduce the prevalence of “atypical” scrapie infection and removing only those exposed sheep that are phenylalanine (F) at codon 141 is scientifically unsound since the disease is known to affect sheep of most other genotypes. Further, sheep with AHQ alleles have a similar risk of infection with “atypical” strains as sheep with F at codon 141. (Luhken, et al., 2007).

• If “atypical” scrapie is included as a listed disease, the surveillance and diagnostic requirements which are needed to identify these cases should be described in detail in both this Chapter and the Manual of Diagnostic Tests and Vaccines for Terrestrial

2

Animals. Data from Europe illustrates that using the proper test(s) is essential for the identification of atypical scrapie (Fediaevsky et al., 2008).

SNIP...

6. Overemphasis on importation and use of bovine meat and bone meal as a route of scrapie transmission: Given that the draft Chapter is not intended to address risk mitigation for BSE in small ruminants, we believe there is an over-emphasis on this potential route of transmission in the current draft.

The United States recommends that the requirements in this chapter be limited to the inclusion of products from sheep and goats (instead of from all ruminants) in feed or feed ingredients intended for consumption by animals.

• The use of products from sheep and goats as feed or feed ingredients for ruminant or non-ruminant animals represent one possible route of transmission (Philippe, et al, 2005) and a source of environmental contamination with the classical scrapie agent. However, this is not the primary route of transmission for the scrapie agent.

• The need for the exclusion of cattle-derived protein or other animal protein to mitigate BSE risk should be based on a country’s BSE risk status and should be addressed in Chapter 2.3.13 of the Code.

SNIP...

14. Failure to provide scientific justification for the list of permitted commodities in Item 1 of Article 2.4.8.1. .

We recommend that the list be re-evaluated and those items that have not been substantiated as presenting no risk be excluded or those with some risk but where the intended use mitigates the risk the use be specified.

• There is no known human health risk associated with scrapie. As such, if meat and meat products for human consumption are included in this list, sheep and/or goat milk intended for human consumption should also be added to the list of permitted commodities in Item 1 of Article 2.4.8.1.

• In the vast majority of sheep infected with classical scrapie, actual infectivity or PrPres has been identified in most tissues including the lymphoreticular system (tonsils, spleen, lymph nodes), the gastrointestinal tract, brain, and spinal cord (Hadlow et. al. 1979; Hadlow et al., 1980; van Kuelen et al., 1996; van Kuelen et al., 1999, Andreoletti et al., 2000; Heggebø et al., 2002; Caplazi et al., 2004). Infectivity and/or PrPres has also been identified in the placenta (see Hourrigan et al., 1979; Onodera et al., 1993; Pattison et al., 1972; Pattison et al., 1974; Race et al., 1998), blood (Hunter et al., 2002; Houston et al. 2008); peripheral nerves (Groschup et al., 1996), muscle (Pattison and Millson, 1962; Andreoletti et al., 2004; Casalone et al., 2005), salivary gland (Hadlow et al., 1980; Vascellari et al., 2007), kidney (Siso et al., 2006), and skin ( Thomzig et al., 2007). In addition, recent work has shown milk and/or colostrum from scrapie infected ewes transmitted the disease to 17 of 18 lambs (Konold et al., 2008).

• The data on the risk of low protein tallow made from scrapie infected tissues particularly for use in milk replacer is limited and some epidemiologic studies suggest an association of milk replacer use with scrapie risk. Taylor et al., 1997 examined the inactivation capacity of different rendering system in regards to scrapie. The presence of infectivity was determined by bioassay into mice. From the onset of this study, it was assumed that tallow was not the vehicle for the transmission of TSE. Hence only 2 tallow samples were examined.

http://www.aphis.usda.gov/import_export/animals/oie/downloads/tahc_mar-sep08/tahc-scrapie-77-mar08_cmt.pdf




• Most critical is that atypical scrapie shows higher prevalence in so-called resistant ARR homozygote and heterozygote genotypes, compared with classical scrapie. • Atypical scrapie has not been found naturally in VRQ/VRQ sheep, although such sheep can be infected artificially. VRQ sheep are, in contrast, highly susceptible to classical scrapie. In the UK, one case of atypical scrapie has been found in VRQ heterozygote (AF141RQ/VRQ) sheep. It is important to ascertain whether or not VRQ-carrying sheep are significantly resistant to infection with atypical scrapie or whether the data might result from a failure to detect PrPres in atypical scrapie due to a different pattern of PrP distribution in tissues. • Increased incidence of atypical scrapie in sheep with PrP alleles carrying the variant phenylalanine (F) at position 141 (leucine(L)/phenylalanine) has also been observed compared with classical scrapie. • It will be important to clarify the genotype effect, particularly in relation to ARR and L141F in transmission studies. • In classical scrapie, there is clear evidence for a PrP genotype effect on tissue distribution patterns of PrPres. This might also be true for atypical scrapie although the data are less complete. 4. Transmission of atypical scrapie It has recently18 been demonstrated that atypical scrapie is experimentally transmissible to mice and sheep, primarily through intracerebral injection. There are some data suggesting that it may also be transmissible orally to sheep of different genotypes. The subgroup noted that challenge experiments with atypical scrapie in sheep were underway in the UK, with one successful intracerebral challenge to date. The subgroup was informed that positive transmission of infectivity from atypical scrapie isolated from sheep with a range of genotypes had been observed in mice. This included ovinised transgenic mice overexpressing the VRQ allele. Nor98 atypical scrapie had also transmitted to ARR ovinised mice, with transmission experiments in AF141RQ ovinised mice planned. Biochemical features of the isolates were maintained after transmission, and were distinct from BSE and classical scrapie. High infectivity titres were observed in brain tissue from atypical scrapie, including from ARR/ARR sheep. Brain transmission experiments in mice carrying the human PrP gene were at an early stage. 18 Le Dur A., Béringue V., Andréoletti O., Reine F., Laï T.H., Baron T., Bratberg B., Vilotte J.- L., Sarradin P., Benestad S.L. and Laude H.(2005) A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes. PNAS 102, 16031-16036

http://www.seac.gov.uk/pdf/positionstatement-sheep-subgroup.pdf




BSE: TIME TO TAKE H.B. PARRY SERIOUSLY

If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf





Thursday, February 23, 2012


Atypical Scrapie NOR-98 confirmed Alberta Canada sheep January 2012


http://transmissiblespongiformencephalopathy.blogspot.com/2012/02/atypical-scrapie-nor-98-confirmed.html





Monday, March 26, 2012


Texas Prepares for Chronic Wasting Disease CWD Possibility in Far West Texas




http://chronic-wasting-disease.blogspot.com/2012/03/texas-prepares-for-chronic-wasting.html




http://chronic-wasting-disease.blogspot.com/






Monday, March 19, 2012


Infectivity in Skeletal Muscle of Cattle with Atypical Bovine Spongiform Encephalopathy


PLoS One. 2012; 7(2): e31449.


http://transmissiblespongiformencephalopathy.blogspot.com/2012/03/infectivity-in-skeletal-muscle-of.html






Thursday, February 23, 2012


EIGHT FORMER SECRETARIES OF AGRICULTURE SPEAKING AT USDA'S 2012 AGRICULTURE OUTLOOK FORUM INDUCTED INTO USA MAD COW HALL OF SHAME


http://madcowusda.blogspot.com/2012/02/eight-former-secretaries-of-agriculture.html






Sunday, March 11, 2012






APHIS Proposes New Bovine Spongiform Encephalopathy Import Regulations in Line with International Animal Health Standards Proposal Aims to Ensure Health of the U.S. Beef Herd, Assist in Negotiations





http://transmissiblespongiformencephalopathy.blogspot.com/2012/03/aphis-proposes-new-bovine-spongiform.html



 

 


TSS

Sunday, November 13, 2011

Atypical Scrapie Isolates Involve a Uniform Prion Species with a Complex Molecular Signature

Atypical Scrapie Isolates Involve a Uniform Prion Species with a Complex Molecular Signature

Dorothea R. Götte1, Sylvie L. Benestad2, Hubert Laude3, Andreas Zurbriggen1, Anna Oevermann1#, Torsten Seuberlich1#*

1 NeuroCentre, National and OIE Reference Laboratories for BSE and Scrapie, Division of Experimental Clinical Research, Vetsuisse Faculty, University of Berne, Berne, Switzerland, 2 Department of Pathology, Norwegian Veterinary Institute, Oslo, Norway, 3 3U892 Virologie Immunologie Moléculaires, Institut National de la Recherche Agronomique, Jouy-en-Josas, France

Abstract Top

The pathobiology of atypical scrapie, a prion disease affecting sheep and goats, is still poorly understood. In a previous study, we demonstrated that atypical scrapie affecting small ruminants in Switzerland differs in the neuroanatomical distribution of the pathological prion protein (PrPd). To investigate whether these differences depend on host-related vs. pathogen-related factors, we transmitted atypical scrapie to transgenic mice over-expressing the ovine prion protein (tg338). The clinical, neuropathological, and molecular phenotype of tg338 mice is similar between mice carrying the Swiss atypical scrapie isolates and the Nor98, an atypical scrapie isolate from Norway. Together with published data, our results suggest that atypical scrapie is caused by a uniform type of prion, and that the observed phenotypic differences in small ruminants are likely host-dependant. Strikingly, by using a refined SDS-PAGE technique, we established that the prominent proteinase K-resistant prion protein fragment in atypical scrapie consists of two separate, unglycosylated peptides with molecular masses of roughly 5 and 8 kDa. These findings show similarities to those for other prion diseases in animals and humans, and lay the groundwork for future comparative research.

snip...

Recently, we reported on a classical scrapie outbreak in a Greek goat flock, in which several animals exhibited a distinct C- and N-terminally ragged PK-resistant PrPres fragment [31]. This peptide demonstrated the same antibody-binding properties, and was estimated to be at similar molecular mass as the 5 kDa PrPres moiety described in the present study. At that time, it was unclear as to which type of prion disease this peptide was related. Our current findings support the idea that this fragment is related to atypical vs. classical scrapie, and that both prion species were present in the Greek flock. Future studies will conduct a direct comparison of these peptides by gradient SDS-PAGE, pending the receipt of material from mouse transmission studies of the Greek isolates.

PrPres peptides of low molecular mass have also been described in other types of prion disease, such as Gerstmann-Sträussler-Scheinker disease [32], [33] and Creutzfeldt-Jakob disease [34], [35] in humans as well as in H-BSE in cattle [36], [37]. Forthcoming directions of research are likely to focus on more precise comparative analyses of truncated PrPres peptides and their role in the biology of human and animal prion diseases...

Citation: Götte DR, Benestad SL, Laude H, Zurbriggen A, Oevermann A, et al. (2011) Atypical Scrapie Isolates Involve a Uniform Prion Species with a Complex Molecular Signature. PLoS ONE 6(11): e27510. doi:10.1371/journal.pone.0027510

Editor: Jason Bartz, Creighton University, United States of America

Received: August 3, 2011; Accepted: October 18, 2011; Published: November 11, 2011

Copyright: © 2011 Götte et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This study was funded by the Swiss Federal Veterinary Office (grant #1.08.13.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

* E-mail: torsten.seuberlich@vetsuisse.unibe.ch

# These authors contributed equally to this work.

see full text ;

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0027510


P02.35

Molecular Features of the Protease-resistant Prion Protein (PrPres) in H-type BSE

Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2; Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden

Western blot analyses of PrPres accumulating in the brain of BSE-infected cattle have demonstrated 3 different molecular phenotypes regarding to the apparent molecular masses and glycoform ratios of PrPres bands. We initially described isolates (H-type BSE) essentially characterized by higher PrPres molecular mass and decreased levels of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type is also distinct from another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low representation of the diglycosylated PrPres band as well as a lower PrPres molecular mass. Retrospective molecular studies in France of all available BSE cases older than 8 years old and of part of the other cases identified since the beginning of the exhaustive surveillance of the disease in 20001 allowed to identify 7 H-type BSE cases, among 594 BSE cases that could be classified as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres, we described a remarkable specific feature with antibodies raised against the C-terminal region of PrP that demonstrated the existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in addition to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another PK-resistant fragment at about 7 kDa was detected by some more N-terminal antibodies and presumed to be the result of cleavages of both N- and C-terminal parts of PrP. These singular features were maintained after transmission of the disease to C57Bl/6 mice. The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band) reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.

http://www.neuroprion.com/pdf_docs/conferences/prion2007/abstract_book.pdf


Sunday, November 13, 2011

Microarray analysis in caudal medulla of cattle orally challenged with bovine spongiform encephalopathy

http://transmissiblespongiformencephalopathy.blogspot.com/2011/11/microarray-analysis-in-caudal-medulla.html


Wednesday, November 09, 2011

Case report Sporadic fatal insomnia in a young woman: A diagnostic challenge: Case Report TEXAS

HOW TO TURN A POTENTIAL MAD COW VICTIM IN THE USA, INTO A HAPPENSTANCE OF BAD LUCK, A SPONTANEOUS MUTATION FROM NOTHING.

OR WAS IT $$$

http://creutzfeldt-jakob-disease.blogspot.com/2011/11/case-report-sporadic-fatal-insomnia-in.html


Tuesday, November 08, 2011

Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008 Vol. 37, No. 3-4, 2011

Original Paper

Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.

http://creutzfeldt-jakob-disease.blogspot.com/2011/11/can-mortality-data-provide-reliable.html


Thursday, July 14, 2011

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

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/histopathological-studies-of-ch1641.html


Monday, June 27, 2011

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

http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html


Thursday, June 23, 2011

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

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html


Monday, June 20, 2011 2011

Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA

http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html


Thursday, June 2, 2011

USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California

http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.html


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

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html


Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE

http://scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.html


Sunday, April 18, 2010

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010

http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html



Monday, April 25, 2011

Experimental Oral Transmission of Atypical Scrapie to Sheep

Volume 17, Number 5-May 2011

http://nor-98.blogspot.com/2011/04/experimental-oral-transmission-of.html


Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html


Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html


Sunday, September 25, 2011

Mad Cow Scaremongers

Mad Cow Scaremongers by Terry S. Singeltary Sr. a review of the TSE prion agent 2003-2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/mad-cow-scaremongers.html


Monday, October 10, 2011

EFSA Journal 2011 The European Response to BSE: A Success Story

snip...

EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.

snip...

http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1


http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf


see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html




http://chronic-wasting-disease.blogspot.com/


http://bse-atypical.blogspot.com/


http://scrapie-usa.blogspot.com/


http://nor-98.blogspot.com/


http://bseusa.blogspot.com/


http://madporcinedisease.blogspot.com/


http://felinespongiformencephalopathyfse.blogspot.com/


http://caninespongiformencephalopathy.blogspot.com/



http://equinespongiformencephalopathy.blogspot.com/


http://transmissible-mink-encephalopathy.blogspot.com/


http://transmissiblespongiformencephalopathy.blogspot.com/


http://creutzfeldt-jakob-disease.blogspot.com/


http://sporadicffi.blogspot.com/


http://prionpathy.blogspot.com/


http://prionopathy.blogspot.com/


http://vcjd.blogspot.com/


http://vcjdblood.blogspot.com/


http://cjdquestionnaire.blogspot.com/2007/11/cjd-questionnaire.html


http://cjdquestionnaire.blogspot.com/


TSS

LAYPERSON

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518