Biochemical Characteristics and PrPSc Distribution Pattern in the Brains of Cattle Experimentally Challenged with H-type and L-type Atypical BSE
Research Article
Biochemical Characteristics and PrPSc Distribution Pattern in the Brains of Cattle Experimentally Challenged with H-type and L-type Atypical BSE
- Grit Priemer,
Affiliation: Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, Germany
X - Anne Balkema-Buschmann,
Affiliation: Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, Germany
X - Bob Hills,
Affiliation: Transmissible Spongiform Encephalopathy Secretariat, Health Canada, Ottawa, Ontario, Canada
X - Martin H. Groschup mail
* E-mail: martin.groschup@fli.bund.de
Affiliation: Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, Germany
X
Abstract
SNIP...
In summary, we could show distinct differences in the anatomical distribution of PrPSc deposition in the brains of cattle affected with the three BSE forms. These differences are sufficiently clear to enable discrimination between classical BSE and atypical BSE, and at least supportive for a differentiation of both atypical BSE forms by Western blot or ELISA rapid test analysis, providing a sufficient number of relevant brain areas are available for analysis. Moreover, these findings are scientifically interesting, since we believe that they mirror the clinical picture observed in cattle affected with either classical or atypical BSE. The differences in protease sensitivity may also have a practical impact on the stability in the environment and possibly on the interspecies transmissibility of the three BSE forms, but these hypothesis need to be elucidated by further analysis.
SNIP...SEE FULL TEXT ;
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0067599
Greetings,
Can we conclude with these findings that the Specified Risk Material SRM ban should be enhanced ?
DO we know for sure the distribution of infectivity and the full spectrum of tissue and muscle infectivity load in these atypical BSE TSE strains ?
I am still hearing nothing on the INBC-BSE type TSE prion disease in UK cattle. I am curious of any further developments, as to exactly what type TSE prion disease in cattle this IBNC was, and if any research is still being down it, and surveillance, if any being done, as well ???
We performed biochemical analyses of the
PrPSc depositions in ten different brain regions. These analyses
verified distinct qualitative and quantitative differences in the anatomical
distribution of PrPSc depositions in the brains of cattle clinically
affected with C-, L- or H-type BSE. While for C-type BSE the PrPSc
depositions are mainly restricted to the brainstem and to a lesser extent to the
cerebellum, whereas cattle affected with both atypical BSE forms showed an
almost even distribution of the pathological prion protein throughout the whole
brain. Although deposition patterns were similar for L- and H-type BSE, L-type
BSE displayed stronger overall intensities. Even though the results from these
areas may be biased by the inoculation route as explained above, the most
pronounced differences were detected in the cortex regions. While cattle
affected with C-type BSE showed only faint signals, even in the end-stage of the
disease, cattle affected with both atypical BSE forms displayed distinctly
higher PrPSc concentrations in the analysed cortex samples. Cattle
affected with all three BSE types showed remarkably high PrPSc
amounts in the midbrain, medulla oblongata and in the thalamus. However, higher
concentrations were determined in the caudal medulla than in cranial medulla for
classical BSE. The opposite was true for atypical BSE, where higher
PrPSc quantities were found in the cranial medulla as opposed to the
caudal medulla. This finding stresses the importance to carefully take the
diagnostic sample from the obex, instead of caudal medulla for BSE rapid
testing, in particular with regard to L-type BSE, because the thalamus, basal
nuclei and midbrain showed stronger involvement than the obex and especially the
caudal medulla. This confirms similar findings that have been reported by others
[7].
The IDEXX HerdChek® EIA is one of the EU-approved rapid tests with a comparably high sensitivity for all three BSE forms [27]. Insofar, we noticed that the optical density values for L-type BSE were all close to the saturation limit and therefore in the non-linear range of the test. A serial dilution approach could help to elucidate the quantity of PrPSc depositions also in L-type BSE affected cattle. However, in our approach we did not use diluted samples in the BSE rapid test, but we adjusted the protein amounts in the Western blot, so that we were able to quantify the PrPSc amounts in this assay.
During the challenge experiment with atypical BSE in cattle, we observed behavioural differences between classical and atypical BSE affected cattle during the end-stage of disease which have already been described in more detail [9]. We noticed that cattle clinically affected with atypical BSE became lethargic and depressive and isolated themselves from the rest of the herd. However, when manipulated during the clinical analysis, these animals turned out to suffer from hind limb ataxia, hyperesthesia (especially in the face) and anxiety, very similar to animals affected with classical BSE. These observations are supported by other reports, where L-type BSE affected cattle showed dullness, depression, exaggerated response to facial touch [28], an initial over-reactivity to tactile stimuli which later yielded a more dull form [9], and a distinct loss of body condition [11]. We therefore postulate that the classical BSE symptoms may be masked or overruled by the depression and loss of condition that at first sight is typical for H- and L-type BSE. This depression may well be caused by the higher grade of involvement of the cerebral cortex in both atypical BSE forms. The different clinical picture may therefore be anchored in the function and phylogenesis of the different involved brain regions.
We then analysed the glycosylation profiles and molecular masses of PK digested PrPSc accumulated in the ten different brain regions. As expected non-glycosylated PrPSc of L-type BSE had a slightly lower molecular mass than that of C-type BSE, whereas non-glycosylated PrPSc of H-type was approximately one kDa higher and all three BSE forms were encoded by a distinct glycoform. However, apart from these general differences, no statistically significant sampling effects were revealed for any of the three BSE types. These findings confirm what has been reported for mouse passaged BSE and scrapie strains [15] and for scrapie in sheep [16], while regional differences have been reported for sCJD [13], [14].
Furthermore, we could show that PrPSc associated with C-type BSE is more resistant towards PK degradation than that of both atypical BSE forms, irrespective of the experimental setup addressing a PK digestion with higher concentrations of up to 1000 µg/ml, or a long-term PK digestion of up to 26 hours. These findings confirm earlier reports [9], [10] regarding the proteinase K (PK) susceptibility of the three BSE forms. These results might have an impact on the actual persistence of BSE infectivity in the environment, since ubiquitous proteases will be more efficient in the degradation of atypical BSE-derived PrPSc as opposed to C-type BSE. Although it has been postulated that PrPSc is not identical to the infectious agent [29], [30], a reduction of the accumulated PrPSc will also reduce the infectivity titre in a sample.
snip...
This study was aimed at the detailed analysis of
the anatomical distribution and the biochemical characteristics of both atypical
BSE forms designated L-type and H-type, as compared to C-type BSE.
At first we used the IDEXX HerdChek® EIA rapid test on the ten brain areas analysed in this study. In cattle challenged with L-type BSE (n = 5) the highest OD values were detected in the midbrain, cranial medulla and thalamus. The OD values determined for these examined brain regions showed relatively even overall OD values ranging between 2.47 and 3.05, which is close to the upper limit of the test, and therefore in the non-linear range. In cattle challenged with H-type BSE (n = 5) the highest OD values could also be detected in the midbrain, cranial medulla and thalamus. Like in L-type BSE affected cattle, the OD values were relatively even, but overall lower than determined for L-type BSE, ranging between 1.60 and 2.68. In contrast to the atypical cases, a more distinct difference was seen between the different brain areas of cattle affected with C-type BSE. For the medulla and midbrain region OD values between 2.61 and 3.09 were determined, as opposed to the OD values for the cortex regions between 0.46 and 1.16. The relative signals in relation to the OD value determined for the cranial medulla as determined by the IDEXX HerdChek® EIA are summarized in Fig. 2.
The IDEXX HerdChek® EIA is one of the EU-approved rapid tests with a comparably high sensitivity for all three BSE forms [27]. Insofar, we noticed that the optical density values for L-type BSE were all close to the saturation limit and therefore in the non-linear range of the test. A serial dilution approach could help to elucidate the quantity of PrPSc depositions also in L-type BSE affected cattle. However, in our approach we did not use diluted samples in the BSE rapid test, but we adjusted the protein amounts in the Western blot, so that we were able to quantify the PrPSc amounts in this assay.
During the challenge experiment with atypical BSE in cattle, we observed behavioural differences between classical and atypical BSE affected cattle during the end-stage of disease which have already been described in more detail [9]. We noticed that cattle clinically affected with atypical BSE became lethargic and depressive and isolated themselves from the rest of the herd. However, when manipulated during the clinical analysis, these animals turned out to suffer from hind limb ataxia, hyperesthesia (especially in the face) and anxiety, very similar to animals affected with classical BSE. These observations are supported by other reports, where L-type BSE affected cattle showed dullness, depression, exaggerated response to facial touch [28], an initial over-reactivity to tactile stimuli which later yielded a more dull form [9], and a distinct loss of body condition [11]. We therefore postulate that the classical BSE symptoms may be masked or overruled by the depression and loss of condition that at first sight is typical for H- and L-type BSE. This depression may well be caused by the higher grade of involvement of the cerebral cortex in both atypical BSE forms. The different clinical picture may therefore be anchored in the function and phylogenesis of the different involved brain regions.
We then analysed the glycosylation profiles and molecular masses of PK digested PrPSc accumulated in the ten different brain regions. As expected non-glycosylated PrPSc of L-type BSE had a slightly lower molecular mass than that of C-type BSE, whereas non-glycosylated PrPSc of H-type was approximately one kDa higher and all three BSE forms were encoded by a distinct glycoform. However, apart from these general differences, no statistically significant sampling effects were revealed for any of the three BSE types. These findings confirm what has been reported for mouse passaged BSE and scrapie strains [15] and for scrapie in sheep [16], while regional differences have been reported for sCJD [13], [14].
Furthermore, we could show that PrPSc associated with C-type BSE is more resistant towards PK degradation than that of both atypical BSE forms, irrespective of the experimental setup addressing a PK digestion with higher concentrations of up to 1000 µg/ml, or a long-term PK digestion of up to 26 hours. These findings confirm earlier reports [9], [10] regarding the proteinase K (PK) susceptibility of the three BSE forms. These results might have an impact on the actual persistence of BSE infectivity in the environment, since ubiquitous proteases will be more efficient in the degradation of atypical BSE-derived PrPSc as opposed to C-type BSE. Although it has been postulated that PrPSc is not identical to the infectious agent [29], [30], a reduction of the accumulated PrPSc will also reduce the infectivity titre in a sample.
snip...
Results
At first we used the IDEXX HerdChek® EIA rapid test on the ten brain areas analysed in this study. In cattle challenged with L-type BSE (n = 5) the highest OD values were detected in the midbrain, cranial medulla and thalamus. The OD values determined for these examined brain regions showed relatively even overall OD values ranging between 2.47 and 3.05, which is close to the upper limit of the test, and therefore in the non-linear range. In cattle challenged with H-type BSE (n = 5) the highest OD values could also be detected in the midbrain, cranial medulla and thalamus. Like in L-type BSE affected cattle, the OD values were relatively even, but overall lower than determined for L-type BSE, ranging between 1.60 and 2.68. In contrast to the atypical cases, a more distinct difference was seen between the different brain areas of cattle affected with C-type BSE. For the medulla and midbrain region OD values between 2.61 and 3.09 were determined, as opposed to the OD values for the cortex regions between 0.46 and 1.16. The relative signals in relation to the OD value determined for the cranial medulla as determined by the IDEXX HerdChek® EIA are summarized in Fig. 2.
Comparable distribution patterns were determined when analysing the same samples by PTA-WB (Fig. 3). However, this method allowed for a more exact quantification of the signal intensities, since the Western blot signals were adjusted to be in the linear range of the VersaDoc™ Imaging System beforehand. In cattle affected with H- and L-type atypical BSE, PrPSc was found to be spread more evenly throughout the whole brain than in C-type BSE affected cattle. The deposition patterns were similar in L- and H-type BSE, but L-type BSE displayed distinctly stronger overall intensities. Analysis of the Western blot signal intensities as compared to the intensity determined for the cranial medulla (set at 100%) revealed high values for L-type BSE in every brain region, which were distinctly higher compared to the other two BSE forms (Fig. 4). Thereby, the highest concentrations of PrPSc could be detected in the brainstem, basal nuclei, thalamus and rhinencephalon, while H-type BSE infected cattle displayed the highest PrPSc concentrations in the brainstem and thalamus. Classical BSE affected animals exhibited lower signal intensities in all brain regions as compared to atypical BSE, with the highest concentrations located in the brainstem. In summary, we were able to identify the three analysed cortex regions as the areas displaying the most obvious differences when comparing classical to atypical BSE. In contrast to classical BSE, both atypical BSE forms are characterized by considerable amounts of PrPSc in the cortex regions.
Analysis of the glycosylation profile
(“glycoprofile”) determined the mean
percentage ratio of the di-, mono- and unglycosylated PrPSc fraction
out of the overall signal. Our study revealed glycoprofiles for classical BSE of
60 : 27 : 13%, for L-type BSE 42 : 36 : 22% and for H-type BSE 55 : 29 : 16% for
the diglycosylated : monoglycosylated : unglycosylated PrPSc fraction
(Fig. 5).
snip...
Conclusions
In summary, we could show distinct differences in the anatomical distribution of PrPSc deposition in the brains of cattle affected with the three BSE forms. These differences are sufficiently clear to enable discrimination between classical BSE and atypical BSE, and at least supportive for a differentiation of both atypical BSE forms by Western blot or ELISA rapid test analysis, providing a sufficient number of relevant brain areas are available for analysis. Moreover, these findings are scientifically interesting, since we believe that they mirror the clinical picture observed in cattle affected with either classical or atypical BSE. The differences in protease sensitivity may also have a practical impact on the stability in the environment and possibly on the interspecies transmissibility of the three BSE forms, but these hypothesis need to be elucidated by further analysis.
snip...
Citation: Priemer G,
Balkema-Buschmann A, Hills B, Groschup MH (2013) Biochemical Characteristics and
PrPSc Distribution Pattern in the Brains of Cattle Experimentally
Challenged with H-type and L-type Atypical BSE. PLoS ONE 8(6): e67599.
doi:10.1371/journal.pone.0067599
Editor: Christopher James Johnson, USGS National Wildlife Health Center, United States of America
Received: January 23, 2013; Accepted: May 20, 2013; Published: June 21, 2013
Copyright: © 2013 Priemer 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: Bob Hills, representing Health Canada (which majorly funded this project), played an active role as a scientist in the development and design of the study. No additional external funding was received for this study.
Competing interests: The authors have declared that no competing interests exist.
Editor: Christopher James Johnson, USGS National Wildlife Health Center, United States of America
Received: January 23, 2013; Accepted: May 20, 2013; Published: June 21, 2013
Copyright: © 2013 Priemer 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: Bob Hills, representing Health Canada (which majorly funded this project), played an active role as a scientist in the development and design of the study. No additional external funding was received for this study.
Competing interests: The authors have declared that no competing interests exist.
Acknowledgments
We are indebted to Mario Ziller and Maya Gussmann from the biomathematics working group at FLI for detailed statistical analysis of our data.Author Contributions
Conceived and designed the experiments: ABB MHG BH. Performed the experiments: GP. Analyzed the data: ABB GP MHG. Contributed reagents/materials/analysis tools: MHG ABB. Wrote the paper: GP ABB MHG.SNIP...SEE FULL TEXT ;
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0067599
Greetings,
Can we conclude with these findings that the Specified Risk Material SRM ban should be enhanced ?
DO we know for sure the distribution of infectivity and the full spectrum of tissue and muscle infectivity load in these atypical BSE TSE strains ?
I am still hearing nothing on the INBC-BSE type TSE prion disease in UK cattle. I am curious of any further developments, as to exactly what type TSE prion disease in cattle this IBNC was, and if any research is still being down it, and surveillance, if any being done, as well ???
Wednesday, May 2, 2012
Saturday, December 15, 2012
Bovine spongiform encephalopathy: the effect of oral exposure dose on
attack rate and incubation period in cattle -- an update 5 December 2012
Tuesday, April 30, 2013
Foodborne Transmission of Bovine Spongiform Encephalopathy to Nonhuman
Primates
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
http://web.archive.org/web/20030327015011/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
Wednesday, July 28, 2010
Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA
Final report
IN CONFIDENCE
BSE ATYPICAL LESION DISTRIBUTION
http://web.archive.org/web/20041226015813/http://www.bseinquiry.gov.uk/files/yb/1993/03/14001001.pdf
Tuesday, November 02, 2010
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only)
diagnostic criteria CVL 1992
Thursday, May 02, 2013
Chronic Wasting Disease (CWD) Texas Important Update on OBEX ONLY TEXTING
Saturday, July 6, 2013
Small Ruminant Nor98 Prions Share Biochemical Features with Human
Gerstmann-Sträussler-Scheinker Disease and Variably Protease-Sensitive
Prionopathy
Research Article
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
*** 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
Saturday, August 4, 2012
Final Feed Investigation Summary - California BSE Case - July 2012
SUMMARY REPORT CALIFORNIA ATYPICAL L-TYPE BSE BOVINE SPONGIFORM
ENCEPHALOPATHY BASE CASE INVESTIGATION JULY 2012
Summary Report BSE 2012
Executive Summary
Saturday, August 4, 2012
Update from APHIS Regarding Release of the Final Report on the BSE
Epidemiological Investigation
in the url that follows, I have posted
SRM breaches first, as late as 2011.
then
MAD COW FEED BAN BREACHES AND TONNAGES OF MAD COW FEED IN COMMERCE up until
2007, when they ceased posting them.
then,
MAD COW SURVEILLANCE BREACHES.
Friday, May 18, 2012
Update from APHIS Regarding a Detection of Bovine Spongiform Encephalopathy
(BSE) in the United States Friday May 18, 2012
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
Tuesday, July 2, 2013
APHIS USDA Administrator Message to Stakeholders: Agency Vision and Goals
Eliminating ALL remaining BSE barriers to export market
Friday, July 19, 2013
PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED Revised
as of April 1, 2013 50# Regular Chicken Feed was found to contain mammalian
protein label does not contain the warning statement
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
October 2009 O.11.3 Infectivity in skeletal muscle of BASE-infected cattle
Silvia Suardi1, Chiara Vimercati1, Fabio Moda1, Ruggerone Margherita1,
Ilaria Campagnani1, Guerino Lombardi2, Daniela Gelmetti2, Martin H. Groschup3,
Anne Buschmann3, Cristina Casalone4, Maria Caramelli4, Salvatore Monaco5,
Gianluigi Zanusso5, Fabrizio Tagliavini1 1Carlo Besta" Neurological
Institute,Italy; 2IZS Brescia, Italy; 33FLI Insel Riems, D, Germany; 4CEA-IZS
Torino, Italy; 5University of Verona, Italy
Background: BASE is an atypical form of bovine spongiform encephalopathy
caused by a prion strain distinct from that of BSE. Upon experimental
transmission to cattle, BASE induces a previously unrecognized disease phenotype
marked by mental dullness and progressive atrophy of hind limb musculature.
Whether affected muscles contain infectivity is unknown. This is a critical
issue since the BASE strain is readily transmissible to a variety of hosts
including primates, suggesting that humans may be susceptible.
Objectives: To investigate the distribution of infectivity in peripheral
tissues of cattle experimentally infected with BASE. Methods: Groups of Tg mice
expressing bovine PrP (Tgbov XV, n= 7-15/group) were inoculated both i.c. and
i.p. with 10% homogenates of a variety of tissues including brain, spleen,
cervical lymph node, kidney and skeletal muscle (m. longissimus dorsi) from
cattle intracerebrally infected with BASE. No PrPres was detectable in the
peripheral tissues used for inoculation either by immunohistochemistry or
Western blot.
Results: Mice inoculated with BASE-brain homogenates showed clinical signs
of disease with incubation and survival times of 175±15 and 207±12 days. Five
out of seven mice challenged with skeletal muscle developed a similar
neurological disorder, with incubation and survival times of 380±11 and 410±12
days. At present (700 days after inoculation) mice challenged with the other
peripheral tissues are still healthy. The neuropathological phenotype and PrPres
type of the affected mice inoculated either with brain or muscle were
indistinguishable and matched those of Tgbov XV mice infected with natural BASE.
Discussion: Our data indicate that the skeletal muscle of cattle
experimentally infected with BASE contains significant amount of infectivity, at
variance with BSE-affected cattle, raising the issue of intraspecies
transmission and the potential risk for humans. Experiments are in progress to
assess the presence of infectivity in skeletal muscles of natural BASE.
see much more here ;
Friday, December 23, 2011
Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate
Model
Volume 18, Number 1—January 2012 Dispatch
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...
2010-2011
When L-type BSE was inoculated into ovine transgenic mice and Syrian
hamster the resulting molecular fingerprint had changed, either in the first or
a subsequent passage, from L-type into C-type BSE. In addition, non-human
primates are specifically susceptible for atypical BSE as demonstrated by an
approximately 50% shortened incubation time for L-type BSE as compared to
C-type. Considering the current scientific information available, it cannot be
assumed that these different BSE types pose the same human health risks as
C-type BSE or that these risks are mitigated by the same protective measures.
This study will contribute to a correct definition of specified risk material
(SRM) in atypical BSE. The incumbent of this position will develop new and
transfer existing, ultra-sensitive methods for the detection of atypical BSE in
tissue of experimentally infected cattle.
Wednesday, March 31, 2010
Atypical BSE in Cattle
To date the OIE/WAHO assumes that the human and animal health standards set
out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE
which include the H-type and L-type atypical forms. This assumption is
scientifically not completely justified and accumulating evidence suggests that
this may in fact not be the case. Molecular characterization and the spatial
distribution pattern of histopathologic lesions and immunohistochemistry (IHC)
signals are used to identify and characterize atypical BSE. Both the L-type and
H-type atypical cases display significant differences in the conformation and
spatial accumulation of the disease associated prion protein (PrPSc) in brains
of afflicted cattle. Transmission studies in bovine transgenic and wild type
mouse models support that the atypical BSE types might be unique strains because
they have different incubation times and lesion profiles when compared to C-type
BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian
hamster the resulting molecular fingerprint had changed, either in the first or
a subsequent passage, from L-type into C-type BSE. In addition, non-human
primates are specifically susceptible for atypical BSE as demonstrated by an
approximately 50% shortened incubation time for L-type BSE as compared to
C-type. Considering the current scientific information available, it cannot be
assumed that these different BSE types pose the same human health risks as
C-type BSE or that these risks are mitigated by the same protective measures.
This study will contribute to a correct definition of specified risk
material (SRM) in atypical BSE. The incumbent of this position will develop new
and transfer existing, ultra-sensitive methods for the detection of atypical BSE
in tissue of experimentally infected cattle.
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...
P.9.21 Molecular characterization of BSE in Canada
Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim
McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre,
Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of
Calgary, Canada
Background: Three BSE types (classical and two atypical) have been
identified on the basis of molecular characteristics of the misfolded protein
associated with the disease. To date, each of these three types have been
detected in Canadian cattle.
Objectives: This study was conducted to further characterize the 16
Canadian BSE cases based on the biochemical properties of there associated
PrPres.
Methods: Immuno-reactivity, molecular weight, glycoform profiles and
relative proteinase K sensitivity of the PrPres from each of the 16 confirmed
Canadian BSE cases was determined using modified Western blot analysis. Results:
Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L
type. The Canadian H and L-type BSE cases exhibited size shifts and changes in
glycosylation similar to other atypical BSE cases. PK digestion under mild and
stringent conditions revealed a reduced protease resistance of the atypical
cases compared to the C-type cases. N terminal- specific antibodies bound to
PrPres from H type but not from C or L type. The C-terminal-specific antibodies
resulted in a shift in the glycoform profile and detected a fourth band in the
Canadian H-type BSE.
Discussion: The C, L and H type BSE cases in Canada exhibit molecular
characteristics similar to those described for classical and atypical BSE cases
from Europe and Japan. This supports the theory that the importation of BSE
contaminated feedstuff is the source of C-type BSE in Canada. *** It also
suggests a similar cause or source for atypical BSE in these countries.
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)
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 largely
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.
P26 TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN
HUMANIZED MOUSE MODELS
Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina
Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi
Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case
Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto
Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany;
4National Veterinary Research Institute, Poland; 5Kansas State University,
Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous
address: USDA National Animal Disease Center, Ames, IA 50010, USA
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). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have
been discovered in three continents since 2004. The first case of naturally
occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006
in the USA. The transmissibility and phenotypes of these atypical BSE
strains/isolates in humans were unknown. We have inoculated humanized transgenic
mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M
isolate. We have found that the atypical BSE-L strain is much more virulent than
the classical BSE-C.*** The atypical BSE-H strain is also transmissible in the
humanized transgenic mice with distinct phenotype, but no transmission has been
observed for the BSE-M isolate so far.
III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE,
DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)
I ask Professor Kong ;
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
END...TSS
Tuesday, November 02, 2010
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only)
diagnostic criteria CVL 1992
Thursday, December 04, 2008 2:37 PM
"we have found that H-BSE can infect humans."
personal communication with Professor Kong. ...TSS
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.
Monday, December 26, 2011
TSS
posted by Terry S. Singeltary Sr. at
12:35 PM
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