Wednesday, January 18, 2012

BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE

February 1, 2012


posted January 18, 2012


BSE in goats can be mistaken for scrapie


Bovine spongiform encephalopathy in goats could be misdiagnosed as scrapie in the absence of appropriate discriminatory tests, and such misidentification occurred at least once before such tests were developed, according to a report released in December.


The article, "Isolation of prion with BSE properties from farmed goat" (Emerging Infectious Diseases 2011;17:2253-2261), indicates BSE can affect small ruminants under natural conditions and that the condition can be misdiagnosed. The agent that causes scrapie is not known to infect humans, but consumption of beef contaminated with the prions that cause BSE is connected with variant Creutzfeldt-Jakob disease, a neurodegenerative disorder in humans.


The report calls for continued extensive surveillance and breeding plans to prevent BSE outbreaks among small ruminants. Such outbreaks could harm public health.


The authors stated in the text that the misdiagnosis occurred in 1990 in the United Kingdom. The case had been identified as suspected BSE in 2006 because differential immunohistochemical analysis of fixed brain tissue produced a signature indistinguishable from BSE. The authors of the recent report used a bioassay to confirm the BSE diagnosis.


The sample collected in 1990 was among 26 historic samples collected from 1984-2002, the report states.


The report indicates the U.K. goat and a goat in France found to have BSE in 2005 both likely became infected through contaminated food supplements.


While BSE lesions are contained mainly within nervous tissue in cattle, the report states "in small ruminants the BSE agent is widely distributed in peripheral tissues and can be transmitted horizontally." Feed ban measures alone would be insufficient for controlling a BSE outbreak in small ruminants, according to the report.


"Also, it would be impossible to prevent BSE from entering the human food chain through consumption of food products derived from small ruminants," the report states.








Saturday, December 3, 2011


Isolation of Prion with BSE Properties from Farmed Goat


Volume 17, Number 12—December 2011


Research


Isolation of Prion with BSE Properties from Farmed Goat


John Spiropoulos , Richard Lockey, Rosemary E. Sallis, Linda A. Terry, Leigh Thorne, Thomas M. Holder, Katy E. Beck, and Marion M. Simmons


Author affiliations: Animal Health and Veterinary Laboratories Agency, Weybridge, Surrey, UK


Abstract


Transmissible spongiform encephalopathies are fatal neurodegenerative diseases that include variant Creutzfeldt-Jakob disease in humans, scrapie in small ruminants, and bovine spongiform encephalopathy (BSE) in cattle. Scrapie is not considered a public health risk, but BSE has been linked to variant Creutzfeldt-Jakob disease. Small ruminants are susceptible to BSE, and in 2005 BSE was identified in a farmed goat in France. We confirm another BSE case in a goat in which scrapie was originally diagnosed and retrospectively identified as suspected BSE. The prion strain in this case was further characterized by mouse bioassay after extraction from formaldehyde-fixed brain tissue embedded in paraffin blocks. Our data show that BSE can infect small ruminants under natural conditions and could be misdiagnosed as scrapie. Surveillance should continue so that another outbreak of this zoonotic transmissible spongiform encephalopathy can be prevented and public health safeguarded.




snip...




Discussion


We confirmed that the agent responsible for TSE in a UK goat, which was initially reported as scrapie in 1990 and subsequently as suspected BSE in 2006 (16), was a BSE agent. This conclusion was based on bioassay of nervous tissue in mice demonstrating similarities of histopathologic lesions, PrPSc mapping in the brain, and WB of PrPSc with those of mice inoculated with BSE from various ovine, caprine, and bovine sources.




From a method perspective, the data suggest that AR, IP, and LP are not optimal bioassay parameters for differentiating TSE sources during first passage because they represent mean values derived from a group of animals that have been inoculated with a specific source. Therefore, a substantial number of animals must die of clinical TSE for these parameters to be meaningful. This finding is a limiting factor in instances in which TSE is diagnosed in only a few animals because of low titer, restricted permissiveness of specific TSE strains in certain laboratory animals, or both. These limitations can be overcome by application of IHC and WB to differentiate BSE from scrapie confidently in individual mice on first passage. Use of IHC has shown that different PrPSc deposits can be identified, and the distribution of each deposit in the brain can be mapped (22,28,32). This approach generates high-resolution data that appear to be specific to individual TSE strains.




The data show that the TSE agents in this study were not altered by the adverse conditions applied to them during histologic procedures. However, titer may decrease, suggesting that the effect of histologic processing is quantitative not qualitative. Therefore, bioassay is a valid approach for identifying BSE in archived histologic material when other techniques are not applicable, as in the current study. Regarding the suitability of different mouse lines for confirming BSE, our data show that any mouse line in which the agent can propagate sufficiently is suitable. An additional requirement at a practical level is the ability to characterize the agent on first passage. In this respect, use of PrP-a mice is preferable because in addition to AR, IP, histopathologic analysis, and PrPSc patterning, WB can also be applied to diagnose BSE. In contrast, its application in PrP-b mice is less informative (33).




These methods can also be applied to analyze bioassay data derived from validated transgenic mouse lines that offer the advantage of higher AR and decreased IP, provided that appropriate transgenic lines are selected and the TSE source and the donor species under investigation are taken into consideration. In this particular instance, our first choices would have been the use of a mouse line overexpressing a bovine transgene in combination with 1 that overexpresses a caprine transgene. At initiation of the study, an established bovinised line was not available to us, and the data generated from the wild-type mice were considered sufficient to identify unequivocally the agent strain. Caprine transgenic mouse lines are still under development and not characterized or widely available. Instead, we used tg338 mice although they show <100% AR and extended IP when inoculated with BSE (26,27). Our data show that this ovinized line offers a feasible alternative for detecting and differentiating caprine TSEs.




The 2 cases of naturally occurring BSE in small ruminants—the 1 reported here and the 1 identified in France (15)—occurred in different countries, during different time periods, and before strict BSE control measures were fully implemented. Therefore, the most likely origin of these 2 cases would be exposure to BSE-contaminated food supplements. Although in France goats constitute 14.3% of the small ruminant population, in the United Kingdom they account for only 0.3% of small ruminants. It is intriguing, therefore, that the only naturally occurring BSE cases in small ruminants in France and particularly in the United Kingdom were detected in goats and not in sheep, although they have also been exposed to contaminated food supplements. A possible explanation could be that goats are generally managed more intensively than sheep and thus might have been exposed to higher doses of the infectious agent because of the more frequent use of concentrates in intensive dairy farming. Similar observations have been reported in cattle, in which the incidence of BSE was significantly higher in dairy herds and in which management is much more intensive than in beef herds (34). In the United Kingdom, most of the commercial goat herds are kept for milk production in a typically intensive production system, similar to dairy cattle.




The BSE case we have confirmed was 1 of 26 historic goat samples examined in the United Kingdom collected during 1984–2002 (16,17). Since 1993, scrapie in goats has been a notifiable disease in the United Kingdom, and since 2005, samples from all suspected cases of TSE in small ruminants are required to be tested for BSE-like features by using WB (19). No BSE cases have been identified, although an intermediate case in a goat was reported and is under investigation by bioassay for final resolution (35,36). This screening of brain samples from all small ruminant cases offers reassurance that BSE is not present in the contemporary small ruminant population. However, application of WB to sheep experimentally co-infected with BSE and scrapie detected only the scrapie agent (37). Also, in contrast to BSE, where infectivity is mainly confined to the nervous system, in small ruminants the BSE agent is widely distributed in peripheral tissues and can be transmitted horizontally (11,38). Therefore, feed ban measures alone would be inadequate to control a BSE outbreak in small ruminants. Also, it would be impossible to prevent BSE from entering the human food chain through consumption of food products derived from small ruminants.




Because TSEs in goats are still a problem, particularly in Mediterranean countries, our data suggest that extensive surveillance and breeding schemes must remain in place to prevent a BSE outbreak in small ruminants and to safeguard public health. This report also highlights several issues regarding the use of mouse bioassay to identify TSE strains. As governing bodies seek confirmation of equivocal cases that are identified worldwide, they must be aware of the limitations, cost, and timescale demands of confirming such cases.




Dr Spiropoulos is a veterinary researcher at Veterinary Laboratories Agency with a particular interest in animal pathology. He is the head of the Mouse Bioassay Team that specializes in pathology of experimental animals. His research interests include neurodegenerative disorders and animal diseases of policy relevance, particularly zoonoses.




Acknowledgments


We thank John Sheehan for tissue retrieval from wax-impregnated tissue blocks; Angel Ortiz-Pelaez for epidemiologic assistance; histopathology employees at Veterinary Laboratories Agency for expert technical support in histopathology and immunohistochemistry; and Animal Services Unit employees at Veterinary Laboratories Agency for expert support with animal procedures and care.




This work was supported by a Department of Environment, Food and Rural Affairs grant (project SE1849).








Saturday, December 3, 2011


Isolation of Prion with BSE Properties from Farmed Goat Volume 17, Number


12—December 2011







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.




J Vet Diagn Invest 21:454-463 (2009)


Nor98 scrapie identified in the United States


Christie M. Loiacono,' Bruce V. Thomsen, S. Mark Hall, Matti Kiupe!, Diane Sutton, Katherine O'Rourke, Bradd Barr, Lucy Anthenill, Deiwyn Keane


Abstract.


A distinct strain of scrapic identified in sheep of Norway in 1998 has since been identified in numerous countries throughout Europe. The disease is known as Nor98 or Not-98-like scrapic. among other names. Distinctions between classic scrapie and Nor98 scrapie are made based on histopathologv and immunodiagnostic results. There are also differences in the epidemiology, typical signalment, and likelihood of clinical signs being observed. In addition, sheep that have genotypes associated with resistance to classic scrapie are not spared from Nor98 disease. The various differences between classic and Nor98 scrapie have been consistently reported in the vast majority of cases described across Europe. The current study describes in detail the patholo gic changes and diagnostic results of the first 6 cases of' Nor98 scrapic disease diagnosed in sheep of the United States.


Key words: Hisiopathology: Nor98: PrP imniunolabeling; scrapie: sheep.


snip...


Results


Case I


The first case identified as consistent with Nor98 scrapie had nonclassic PrP distribution in brain tissue, no PrPSC in lymph tissue, and nonclassic migration of protein bands on a Western blot test. The animal was an aged, mottled-faced ewe that was traced back to a commercial flock in Wyoming. ...


Case 2


The second case was a clinically normal 8-year-old Suffolk ewe that had been in a quarantined flock for 5 years at a USDA facility in Iowa.


Case 3


A 16-year-old, white-faced, cross-bred wether was born to a black-faced ewe. He lived his entire life as a pet on a farm in California.


Case 4


The fourth case of Nor98 scrapie was identified in an approximately 8-year-old Dorset ewe that was born into a flock of approximately 20 ewes in Indiana.


Case 5


The fifth case was a clinically normal, approximately 3-year-old, white-faced, cross-bred ewe from an approximately 400 head commercial flock in Minnesota.


Case 6


The sixth case of Nor98 scrapie was identified in a 4-year-old, white-faced ewe that was purchased and added to a commercial flock in Pennsylvania


snip...


see full text ;









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







Sunday, October 3, 2010


Scrapie, Nor-98 atypical Scrapie, and BSE in sheep and goats North America, who's looking ?






Thursday, November 18, 2010


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






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...










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




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




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).




Wednesday, February 16, 2011


IN CONFIDENCE


SCRAPIE TRANSMISSION TO CHIMPANZEES


IN CONFIDENCE






Sunday, April 18, 2010


SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010




Monday, April 25, 2011


Experimental Oral Transmission of Atypical Scrapie to Sheep


Volume 17, Number 5-May 2011




Sunday, March 28, 2010


Nor-98 atypical Scrapie, atypical BSE, spontaneous TSE, trade policy, sound science ?




Monday, November 30, 2009


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




I strenuously urge the USDA and the OIE et al to revoke the exemption of the legal global trading of atypical Nor-98 scrapie TSE. ...TSS


Friday, February 11, 2011


Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues




Thursday, July 14, 2011


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




Monday, June 27, 2011


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




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. ...




Thursday, June 2, 2011


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




Monday, June 20, 2011 2011


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




Monday, June 27, 2011


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






Sunday, December 12, 2010


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




Monday, November 22, 2010


Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control


REVIEW ARTICLES




Sunday, April 18, 2010


SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010




Wednesday, January 19, 2011


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






Sunday, March 27, 2011


SCRAPIE USA UPDATE FEBRUARY 2011




Thursday, June 2, 2011


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










Scrapie Nor-98 like case in California FY 2011 AS of December 31, 2010.


Scrapie cases in goats FY 2002 - 2011 AS of December 31, 2010 Total goat cases = 21 Scrapie cases, 0 Nor-98 like Scrapie cases (21 field cases, 0 RSSS cases)


Last herd with infected goats disignated in FY 2008 Michigan 8 cases




UPDATE PLEASE NOTE ;


AS of June 30, 2011,


snip...


INCLUDING 10 POSITIVE GOATS FROM THE SAME HERD (FIGURE 7).


snip...


see updated APHIS scrapie report ;




Tuesday, February 01, 2011


Sparse PrP-Sc accumulation in the placentas of goats with naturally acquired scrapie


Research article


snip...


Date: Tuesday, February 01, 2011 5:03 PM


To: Mr Terry Singeltary


Subject: Your comment on BMC Veterinary Research 2011, 7:7


Dear Mr Singeltary


Thank you for contributing to the discussion of BMC Veterinary Research 2011, 7:7 .


Your comment will be posted within 2 working days, as long as it contributes to the topic under discussion and does not breach patients' confidentiality or libel anyone. You will receive a further notification by email when the posting appears on the site or if it is rejected by the moderator.


Your posting will read:


Mr Terry Singeltary, retired Scrapie cases Goats from same herd USA Michigan


Comment: " In spite of the poorly defined effects of PRNP genetics, scrapie strain, dose, route and source of infection, the caprine placenta may represent a source of infection to progeny and herd mates as well as a source of persistent environmental contamination. "


Could this route of infection be the cause of the many cases of Goat scrapie from the same herd in Michigan USA ?


Has this been investigated ?


(Figure 6) including five goat cases in FY 2008 that originated from the same herd in Michigan. This is highly unusual for goats, and I strenuously urge that there should be an independent investigation into finding the common denominator for these 5 goats in the same herd in Michigan with Scrapie. ...


Kind Regards, Terry


Thursday, January 07, 2010


Scrapie and Nor-98 Scrapie November 2009 Monthly Report Fiscal Year 2010 and FISCAL YEAR 2008




In FY 2010, 72 cases of classical Scrapie and 5 cases of Nor-98 like Scrapie were confirmed...




Scrapie Nor-98 like case in California FY 2011 AS of December 31, 2010.


Scrapie cases in goats FY 2002 - 2011 AS of December 31, 2010 Total goat cases = 21 Scrapie cases, 0 Nor-98 like Scrapie cases (21 field cases, 0 RSSS cases)


Last herd with infected goats disignated in FY 2008 Michigan 8 cases




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




atypical scrapie just MAY be contagious, and MAY, IN FACT, NOT be a spontaneous degenerative condition of older sheep, AND with science transmission studies to date, there is more evidence that typical scrapie MAY transmit to man. and to imagine that the USDA and the OIE now base their scientific human and animal risk factors on MAY FACTORS, is really unbelieveable, unacceptable, and shows just how corrupt this global TSE livestock food system is, thanks to the OIE and the USDA. ...TSS




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.










Thursday, June 23, 2011


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




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"




Sunday, June 26, 2011


Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque






Friday, December 23, 2011


Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model


Volume 18, Number 1—January 2012 Dispatch




Saturday, July 23, 2011


CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE




Saturday, November 6, 2010


TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU


Berne, 2010 TAFS INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation




Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR>


Prion disease update 2010 (11) PRION DISEASE UPDATE 2010 (11)






TSS

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