Cattle with the E211K polymorphism, and gCJD linked to a glutamic acid to lysine substitution at codon 200 (E200K) of PRNP, what if?
Cattle with the E211K polymorphism, and gCJD linked to a glutamic acid to lysine substitution at codon 200 (E200K) of PRNP, what if?
i believe science has shown that to many times with Transmissible Spongiform Encephalopathy TSE PrP disease, and all of the variants, strains, too many times scientists are to quick ruling out potential causes or links, before actually proving their findings. i believe that science shows that feed can potentially play a role in Cattle with the E211K polymorphism, and there from, humans with gCJD linked to a glutamic acid to lysine substitution at codon 200 (E200K) of PRNP, and or iatrogenic events, there from, what if?
AI overview
The E211K mutation in the bovine PRNP gene is a critical, rare, and heritable genetic variation associated with H-type bovine spongiform encephalopathy (H-BSE). It is considered to be the bovine equivalent to the human PRNP E200K mutation, which causes the most common form of genetic Creutzfeldt-Jakob disease (gCJD).
Genetic Creutzfeldt-Jakob disease linked to the E200K mutation: a large cohort study Published: 13 January 2026
Abstract
Creutzfeldt-Jakob disease (CJD), the most common human prion disease, is an invariably fatal neurodegenerative disorder affecting 1.5 cases per million individuals per year. About 10–15% of the human prion diseases are caused by a pathogenic variant in the prion protein (PrP) gene (PRNP), and the most common genetic human prion disease is CJD (gCJD) linked to a glutamic acid to lysine substitution at codon 200 (E200K) of PRNP. The polymorphic codon 129 methionine (M)/valine (V) genotype has a strong effect on disease phenotype. In the present study, we retrospectively evaluated many features of gCJD E200K cases with respect to the 129MV polymorphism, type of scrapie prion protein (PrPSc), demographic, clinical, laboratory, histopathology, and molecular features, including western blot examination and real-time quaking-induced conversion assay. Analyses were also performed to determine statistically significant features between E200K haplotypes (e.g., codon 129 genotype in cis with the mutated allele) and codon 129 genotypes. This study found that codon 129 polymorphism affects several disease features of gCJD E200K. Specifically, histopathologic differences were found between patients with different 129 haplotypes and genotypes. We have identified five groups or subtypes of E200K associated with either PrPSctype 1 or 2. Other E200K cases showed mixed (i) PrPSc types or (ii) pathological features of 129 M and 129 V haplotypes. To our knowledge, this study describes the largest cohort of 177 E200K cases and provides new insight into the wide range of phenotypes associated with this common CJD genetic variant.
Conclusions: Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material.
Funded by: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agricultural Research Service. The funders of the work did not influence study design, data collection and analysis, decision to publish, or preparation of the manuscript.
"Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material."
https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf
Title: Short incubation periods of atypical H-type BSE to cattle with EK211 and KK211 prion protein genotypes after intracranial inoculation
First Report of the Potential Bovine Spongiform Encephalopathy (BSE)-Related Somatic Mutation E211K of the Prion Protein Gene (PRNP) in Cattle
Sae-Young Won 1,2,† , Yong-Chan Kim 1,2,† and Byung-Hoon Jeong 1,2,*
1 Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk 54531, Korea; gkfh32@jbnu.ac.kr (S.-Y.W.); kych@jbnu.ac.kr (Y.-C.K.) 2 Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, Jeonbuk 54896, Korea * Correspondence: bhjeong@jbnu.ac.kr; Tel.: +82-63-900-4040; Fax: +82-63-900-4012 † These authors contributed equally to this work.
Received: 25 May 2020; Accepted: 11 June 2020; Published: 15 June 2020
Abstract: Bovine spongiform encephalopathy (BSE) is a prion disease characterized by spongiform degeneration and astrocytosis in the brain. Unlike classical BSE, which is caused by prion-diseasecontaminated meat and bone meal, the cause of atypical BSE has not been determined. Since previous studies have reported that the somatic mutation in the human prion protein gene (PRNP) has been linked to human prion disease, the somatic mutation of the PRNP gene was presumed to be one cause of prion disease. However, to the best of our knowledge, the somatic mutation of this gene in cattle has not been investigated to date. We investigated somatic mutations in a total of 58 samples, including peripheral blood; brain tissue including the medulla oblongata, cerebellum, cortex, and thalamus; and skin tissue in 20 individuals from each breed using pyrosequencing. In addition, we estimated the deleterious effect of the K211 somatic mutation on bovine prion protein by in silico evaluation tools, including PolyPhen-2 and PANTHER. We found a high rate of K211 somatic mutations of the bovine PRNP gene in the medulla oblongata of three Holsteins (10% ± 4.4%, 28% ± 2%, and 19.55% ± 3.1%). In addition, in silico programs showed that the K211 somatic mutation was damaging. To the best of our knowledge, this study is the first to investigate K211 somatic mutations of the bovine PRNP gene that are associated with potential BSE progression.
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3. Discussion
Although the number of classical BSE cases caused by contaminated meat and bone meal has decreased dramatically due to global efforts, the number of atypical BSE cases increased [30,31]. In humans, genetic prion disease makes up approximately 10% to 15% of cases with germline mutations of the PRNP gene [19]. However, although sporadic prion disease accounts for 85% of human prion diseases, the exact cause of sporadic prion disease has not been revealed to date. In recent studies, somatic mutations in the PRNP gene have been identified in human sporadic prion diseases and have been suggested as one cause of sporadic prion disease. In cattle, the E211K germline mutation of the bovine PRNP gene was first reported in the United States in 2006 [25–27]. The bovine E211K mutation showed homology in the region with the E200K mutation of the human PRNP gene, which is most frequently observed in human familial prion diseases [20,22]. Thus, we investigated the E211K somatic mutation of the bovine PRNP gene, which may be considered a novel risk factor for BSE in Korean cattle.
In our previous study, the germline mutation at codon 211 of the bovine PRNP gene was not observed in 384 Hanwoo cattle and 152 Holstein cattle [5]. Remarkably, we found high rates of K211 somatic mutation of the bovine PRNP gene in three Holstein cattle (Table 3). In Korea, since classical and atypical BSEs have never been reported in Hanwoo, the absence of K211 somatic mutations in Hanwoo is notable. In addition, although we tested K211 somatic mutations, including whole blood and four brain regions, somatic mutations of this gene were detected only in the medulla oblongata. The expected level of K211 mutations of the bovine PRNP gene, which can initiate atypical BSE, is elusive. A previous study in early-onset Alzheimer’s disease reported that 14% of mutations of the presenilin 1 (PSEN1) gene in brain cells are responsible for the initiation of this disease [32]. In another study, the somatic mutations of amyloid precursor protein (APP), nicastrin (NCSTN), sortilin-related receptor (SORL1), and microtubule affinity-regulating kinase 4 (MARK4) were observed in sporadic Alzheimer’s disease patients in 0.2–10.5% [33]. We observed three samples containing over 10% K211 mutations (Figure 3). Thus, BSE inspection of these samples seems essential to elucidate the expected level of K211 mutations of the PRNP gene, which can initiate atypical BSE in the future. According to previous studies, since the medulla oblongata showed a prominent accumulation of PrPSc, the diagnosis of BSE was performed in the medulla oblongata region [34]. However, since the three Holstein cattle carrying the K211 somatic mutation in the medulla oblongata were not investigated as to whether K211 somatic mutation could be observed in other brain regions, it is difficult to conclude that this somatic mutation was only found in the medulla oblongata. In addition, since atypical BSE has shown to be a prominent brain pathology in the frontal cortex [17,18], if the atypical BSE was caused by a somatic mutation of the PRNP gene, it is expected that the somatic mutation was also found in the cerebral cortex. Thus, further investigation of the K211 somatic mutation is highly desirable in other brain regions, including the cerebral cortex of the three Holstein cattle carrying K211 somatic mutation in the medulla oblongata. We also performed in silico analysis using PolyPhen-2 and PANTHER to evaluate whether the mutation of K211 of the bovine PRNP gene affects the bovine PrP protein. Notably, the K211 somatic mutation of the bovine PRNP gene was evaluated as “damaging”. Since PolyPhen-2 can estimate structural variation, the prediction can be interpreted that K211 somatic mutation can contribute to the conformational change to the susceptible structure of the PrPSc. In addition, the wild-type PrP with E211 allele was predicted to be of high preservation time (361, Table 4) and K211 somatic mutation was estimated to be deleterious by using the PANTHER program. The prediction of PANTHER indicated that K211 mutation has been very rare and has not been observed in ancestral proteins for a long time. To confirm the effect of K211 mutation on prion disease, investigation of symptoms of prion disease in bovine PrP transgenic mice carrying the K211 allele is highly desirable in the future. It seems possible that a high somatic mutation rate contributes to sporadic prion disease in cattle.
Previous studies have reported that prion disease is accelerated in transgenic (Tg) mice expressing wild-type bank vole prion protein (BVPrP) containing E200K, which is associated with human familial CJD [35]. In addition, recent studies have demonstrated that a human PrP Tg mouse model with the E200K mutation can lead to spontaneous prion disease [36]. In cattle, the E211K mutation, which is a homologous region of human E200K, is expected to have a deleterious effect on BSE, and several in silico programs in the present study are expected to cause structural changes in the bovine prion protein (Table 4). To determine whether the E211K mutation affects the susceptibility to prion disease, brain samples with high mutation rates of E211K should be investigated by protein misfolding cyclic amplification (PMCA) or Western blotting (WB) in the future.
Canadian 2021 H-type Bovine Spongiform Encephalopathy case associated with a novel E211K polymorphism in prion protein gene Waqas Tahir , Sandor Dudas , Renee Anderson , Jianmin Yang , Sarah Bogart , Kristina Santiago-Mateo , show all Pages 36-49 | Received 20 Feb 2025, Accepted 22 May 2025, Published online: 04 Aug 2025 Cite this article https://doi.org/10.1080/19336896.2025.2511933 CrossMark Logo.svg CrossMark
Article contents
Related research Full Article Figures & data References Supplemental Citations Metrics Licensing Reprints & Permissions View PDF(open in a new window)View EPUB(open in a new window)Share Back to Top ABSTRACT Bovine Spongiform Encephalopathy (BSE) is a fatal neurodegenerative disease in cattle which can be either classical BSE (C-BSE) or atypical BSE (including H-BSE and L-BSE). Here, we report the results of our analyses of an H-BSE case found in Canada in 2021, indicating restriction of the pathological agent (PrPSc) mainly to the central nervous system with no or occasional weak involvement of peripheral tissues. Importantly, a non-synonymous mutation at codon 211 of the PRNP gene was detected and confirmed to be present as a germline mutation. This is the first case of BSE in Canada with a predisposing E211K mutation.
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Somatic mutations in the PRNP gene at codon D178N in sporadic CJD and P102L associated with sporadic Gerstmann – Sträussler – Scheinker (GSS) syndrome have also been documented in humans 46, 47.
Thursday, December 04, 2008 3:37 PM
Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment
IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....
Professor Kong reply ;
.....snip
As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete. Thanks for your interest.
Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA
P.4.23 Transmission of atypical BSE in humanized mouse models
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA
Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were argely undefined.
Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice.
Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.
Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time. The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.
Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
P.4.23 Transmission of atypical BSE in humanized mouse models
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA
Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were argely undefined.
Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice.
Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.
Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time. The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.
Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
see full text ;
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full test Singeltary et al PLOS
THURSDAY, JULY 20, 2017
USDA OIE Alabama Atypical L-type BASE Bovine Spongiform Encephalopathy BSE animal feeds for ruminants rule, 21 CFR 589.200
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.
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)
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
Thursday, July 24, 2014
*** Protocol for further laboratory investigations into the distribution of infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA New protocol for Atypical BSE investigations
Thursday, July 24, 2014
*** Protocol for further laboratory investigations into the distribution of infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA New protocol for Atypical BSE investigations
THURSDAY, FEBRUARY 14, 2013
Unique Properties of the Classical Bovine Spongiform Encephalopathy Strain and Its Emergence From H-Type Bovine Spongiform Encephalopathy Substantiated by VM Transmission Studies
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)
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
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.
PPo4-15:
A Surprisingly High Number of the Plaque-Like VV sCJD Subtype Among the Polish sCJD-is There a Connection with BASE?
Beata Sikorska and Pawel P. Liberski Department of Molecular Pathology and Neuropathology; Medical University of Lodz; Lodz, Poland
Recently described bovine amyloidotic spongiform encephalopathy (BASE) or L type BSE-was is overrepresented in Poland (15% of all cases of BSE). Moreover, the number of BASE cases in Poland per million bovines is the highest in Europe. A potential human risk from BASE is evident from experimental transmission to "humanized" transgenic animals and primates. Taking into consideration that non-human primate inoculated with BASE had a shorter incubation period than monkeys infected with classical BSE, and that humanized Tg mice have been found to be highly susceptible to infection with atypical form of BSE, it seems probable that BASE may be more pathogenic for humans than BSE, but the transmitted disease may differ from BSE-derived vCJD. Among 47 cases which have been diagnosed as definite in our laboratory, in 19 cases complete histopathological examination and codon 129 status were available. On the basis of the histological pattern and codon 129 status the cases of sCJD were divided into subtypes according to the Parchi&Gambetti classification. The results are as follows: type 1 (MMorMV)- 42%, type 2 (VV)-32%, type 3 (MV)-10.5%, type 4c (MM)- 10.5% and type 5 (VV)-5 %. Although the number of cases is too low to conclude a significantly different distribution of sCJD subtypes in Polish population those data show surprisingly high number of the plaque-like VV sCJD subtype. Interestingly, it was shown before that Tg mice inoculated with BASE showed granular and plaque-like aggregates or PrPSc in brains resembling those observed in VV2 subtype of sCJD.
PPo2-26:
Transmission of Classical and Atypical (L-type) Bovine Spongiform Encephalopathy (BSE) Prions to Cynomolgus macaques
Fumiko Ono,1 Yoshio Yamakawa,2 Minoru Tobiume,3 Yuko Sato,3 Harutaka Katano,3 Kenichi Hagiwara,2 Iori Itagaki,1 Akio Hiyaoka,1 Katuhiko Komatuzaki,1 Yasunori Emoto,1 Hiroaki Shibata,4 Yuichi Murayama,5 Keiji Terao,4 Yasuhiro Yasutomi4 and Tetsutaro Sata3
1The Corporation for Production and Research of Laboratory Primates; Tsukuba City, Japan; 2Departments of Cell Biology and Biochemistry; and 3Pathology; National Institute of Infectious Diseases; Tokyo, Japan; 4Tsukuba Primate Research Center; National Institute of Biomedical Innovation; Tsukuba City, Japan; 5Prion Disease Research Team; National Institute of Animal Health; Tsukuba City, Japan
Key words: L-type BSE, cBSE, cynomolgus macaques, transmission
BSE prion derived from classical BSE (cBSE) or L-type BSE was characterized by inoculation into the brain of cynomolgus macaques. The neurologic manifestation was developed in all cynomolgus macaques at 27-43 months after intracerebral inoculation of brain homogenate from cBSE-affected cattle (BSE JP/6). Second transmission of cBSE from macaque to macaque shortened incubation period to 13-18 months. cBSE-affected macaques showed the similar clinical signs including hyperekplexia, tremor and paralysis in both primary and second transmission.
Two macaques were intracerebrally inoculated brain homogenate from the L-type BSE-affected cattle (BSE JP/24). The incubation periods were 19-20 months in primary transmission.
The clinical course of the L-type BSE-affected macaques differed from that in cBSE-affected macaques in the points of severe myoclonus without hyperekplexia. The glycoform profile of PrPSc detected in macaque CNS was consistent with original pattern of either cBSE or L-typeBSE PrPSc, respectively. Although severe spongiform change in the brain was remarkable in all BSE-affected macaques, severe spongiform spread widely in cerebral cortex in L-type BSE-affected macaques. Heavy accumulation of PrPSc surrounded by vacuola formed florid plaques in cerebral cortex of cBSE-affected macaques. Deposit of PrPSc in L-type BSE-affected macaque was weak and diffuse synaptic pattern in cerebrum, but large PrPSc plaques were evident at cerebellum. MRI analysis, T2, T1, DW and flair sequences, at the time of autopsy revealed that brain atrophy and dilatation of cerebral ventricles were significantly severe in L-type BSE-affected macaques. These results suggest that L-type BSE is more virulent strain to primates comparing to cBSE.
SP1-4:
Evidence from Molecular Strain Typing
Gianluigi Zanusso Department of Neurological and Visual Sciences; Section of Clinical Neurology; University of Verona; Verona, Italy
Key words: molecular analysis, strain typing, atypical BSE, CJD
In 2001, active surveillance for bovine spongiform encephalopathy (BSE) led to the discovery of atypical BSE phenotypes in aged cattle distinct from classical BSE (C-type). These atypical BSE cases had been classified as low L-type (BASE) or high H-type BSE based on the molecular mass and the degree of glycosylation of of the pathological prion protein (PrPSc). Transmission studies in TgBov mice showed that H-type BSE, C-type BSE and BASE behave as distinct prion strains with different incubation periods, PrPSc molecular patterns and pathological phenotypes. A still unclear issue concerns the potential transmissibility and phenotypes of atypical BSEs in humans. We previously indicated that BASE was similar to a distinct subgroup of sporadic form of Creutzfeldt-Jakob disease (sCJD) MV2, based on molecular similarities and on neuropathological pattern of PrP deposition. To investigate a possible link between BASE and sCJD, Kong et al. and Comoy et al. experimentally inoculated TgHu mice (129MM) and a non-human primate respectively, showing in both models that BASE was more virulent compare to BSE. Further, non-human primate reproduced a clinical phenotype resembling to that of sCJD subtype MM2. Here, we presented a comparative analysis of the biochemical fingerprints of PrPSc between the different sCJD subtypes and animal TSEs and after experimental transmission to animals.
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data.
***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison.
The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers.. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
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The tissue distribution of infectivity in CWD‐infected cervids is now known to extend beyond CNS and lymphoid tissues. While the removal of these specific tissues from the food chain would reduce human dietary exposure to infectivity, exclusion from the food chain of the whole carcass of any infected animal would be required to eliminate human dietary exposure.
PLOS ONE Journal
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure
Terry S. Singeltary Sr., 03 Jul 2015 at 16:53 GMT
***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.
***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.
*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***
Greetings Plos et al,
in reference to;
‘’A Naturally Occurring Bovine Tauopathy Is Geographically Widespread in the UK’’
I kindly wish to comment please, as follows.
I was stunned by this report.
This Research Report should have been titled ;
‘’It Appears A Naturally Occurring Bovine Tauopathy Is Geographically Widespread in the UK’’
>>>Thus IBNC _appears_ to be the first naturally occurring and geographically widespread tauopathy in a species other than humans.<<<
>>>IBNC _appear_ to lack intracellular neurofibrillary tangles,<<<
>>>Thus IBNC _appears_ to be the first naturally occurring and geographically widespread tauopathy in a species other than humans<<<
>>>IBNC appears to be a complex proteinopathy with evidence for additional secondary accumulation of alpha synuclein, ubiquitin, and possibly PrP [5]. <<<
>>>however, it appears to represent a naturally-occurring predominantly 3R tauopathy in a non-primate species.<<<
>>>In the absence of any specific aetiological cause of IBNC yet identified, and based on the existing epidemiology and presence of P-tau we have considered the possibility that IBNC might also have a significant environmental component. Epidemiological investigations to explore usage of herbicides, insecticides, parasiticides and other chemicals used in agriculture would be helpful in future investigations of IBNC and might provide further insight into some causes of neurodegeneration in man.<<<
This is supposition at best in my opinion, and at worse, I will refrain from comment.
Too many _appears_ , appears this, appears that.
Too many _In the absence of any specific aetiological cause of IBNC yet identified_
is this what science has come to?
has science become some entwined with corporate special interest, do we change science now?
I believe that is far too early to rule out IBNC as a Transmissible Spongiform Encephalopathy TSE prion disease, either of typical or typical strain.
it can be argued that there is potential for Alzheimer’s to be a low dose TSE Prion disease ;
***> 2026 Chronic Wasting Disease CWD, Transmissible Spongiform Encephalopathy TSE, Prion PrP
***> CWD Action Plan National Program 103 Animal Health 2022-2027 UPDATE JANUARY 2026
***> SCRAPIE TSE Prion USA RAPID RESPONSE URGENT UPDATES DECEMBER 25, 2025
***> CWD vs Scrapie Urgent Update
***> 2026 USDA EXPLANATORY NOTES, APHIS, CWD, BSE, Scrapie, TSE, Prion
Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies
Location: Virus and Prion Research
2025 Annual Report
USDA National Scrapie Program History and Bovine Spongiform Encephalopathy BSE TSE Update 2025 and history there from
APHIS USDA Captive CWD Herds Update by State December 2025 Update
TUESDAY, SEPTEMBER 30, 2025
USDA EXPLANATORY NOTES ANIMAL AND PLANT HEALTH INSPECTION SERVICE 2025-2014 CHRONIC WASTING DISEASE CWD TSE CERVID
TUESDAY, SEPTEMBER 30, 2025
USDA National Scrapie Program History and Bovine Spongiform Encephalopathy BSE TSE Update 2025
TUESDAY, SEPTEMBER 30, 2025
USDA National Scrapie Program History and Bovine Spongiform Encephalopathy BSE TSE Update 2025
THURSDAY, JANUARY 08, 2026
Confucius Ponders, what about Wild Pigs (Sus scrofa) and CWD TSE Prion, and the Environment, what if?
Confucius Ponders, what about Wild Pigs (Sus scrofa), they can cover some distance rather quickly, what about Wild Pigs (Sus scrofa) digging up the terrain, and as they do it, what if these Wild Pigs (Sus scrofa) were exposed to CWD TSE Prion, and then they go on exposing and saturating the land with CWD TSE Prion, then the soil becomes contaminated with CWD TSE Prion, then what about the plants that grow from that soil for the decades to come, what if???
WEDNESDAY, OCTOBER 15, 2025
US NATIONAL PRION DISEASE PATHOLOGY SURVEILLANCE CENTER CJD TSE REPORT 2025
FRIDAY, NOVEMBER 21, 2025
While no one was watching: Tenuous status of CDC prion unit, risk of CWD to people worry scientists
FRIDAY, NOVEMBER 21, 2025
While no one was watching: Tenuous status of CDC prion unit, risk of CWD to people worry scientists
SATURDAY, JANUARY 10, 2026
Neuropsychiatric symptoms in sporadic Creutzfeldt-Jakob disease, a review
terry
posted by Terry S. Singeltary Sr. at
12:02 PM
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