Enhanced Virulence of Sheep-Passaged Bovine Spongiform Encephalopathy Agent
Is Revealed by Decreased Polymorphism Barriers in Prion Protein Conversion
Studies
Jan Priema, Jan P. M. Langevelda, Lucien J. M. van Keulena, Fred G. van
Zijderveldb, Olivier Andreolettic and Alex Bossersa
+ Author Affiliations aDepartment of Infection Biology, Central Veterinary
Institute of Wageningen UR, Lelystad, The Netherlands bDepartment of
Bacteriology and TSEs, Central Veterinary Institute of Wageningen UR, Lelystad,
The Netherlands cUMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole
Nationale Vétérinaire de Toulouse, France
ABSTRACT
Bovine spongiform encephalopathy (BSE) can be efficiently transmitted to
small ruminants (sheep and goats) with certain prion protein (PrP) genotypes.
Polymorphisms in PrP of both the host and donor influence the transmission
efficiency of transmissible spongiform encephalopathies (TSEs) in general. These
polymorphisms in PrP also modulate the PrP conversion underlying TSE agent
replication. Here we demonstrate that single-round protein misfolding cyclic
amplification (PMCA) can be used to assess species and polymorphism barriers at
the molecular level. We assessed those within and between the ovine and bovine
species in vitro using a variety of natural scrapie and experimentally generated
cross-species BSE agents. These BSE agents include ovBSE-ARQ isolates (BSE
derived from sheep having the ARQ/ARQ PrP genotype), and two unique BSE-derived
variants: BSE passaged in VRQ/VRQ sheep and a cow BSE agent isolate generated by
back-transmission of ovBSE-ARQ into its original host. PMCA allowed us to
quantitatively determine PrP conversion profiles that correlated with known in
vivo transmissibility and susceptibility in the two ruminant species in which
strain-specific molecular signatures, like its molecular weight after protease
digestion, were maintained. Furthermore, both BSE agent isolates from ARQ and
VRQ sheep demonstrated a surprising transmission profile in which efficient
transmissions to both sheep and bovine variants was combined. Finally, all data
support the notion that ARQ-derived sheep BSE points to a significant increase
in virulence compared to all other tested scrapie- and BSE-derived variants
reflected by the increased conversion efficiencies of previously inefficient
convertible PrP variants (including the so-called “resistant” sheep ARR
variant).
IMPORTANCE Prion diseases such as scrapie in sheep and goats, BSE in
cattle, and Creutzfeldt-Jakob disease (CJD) in humans are fatal
neurodegenerative diseases caused by prions. BSE is known to be transmissible to
a variety of hosts, including sheep and humans. Based on the typical BSE agent
strain signatures and epidemiological data, the occurrence of a novel variant of
CJD in humans was linked to BSE occurrence in the United Kingdom. Measures,
including genetic selection of sheep toward less susceptible PrP genotypes, have
been implemented to lower the risk of BSE transmission into sheep, since the
disease could potentially spread into a natural reservoir. In this study, we
demonstrated using molecular PrP conversion studies that when BSE is first
transmitted through sheep, the host range is modified significantly and the PrP
converting potency increased, allowing the ovine BSE to transmit more
efficiently than cow BSE into supposedly less susceptible hosts.
FOOTNOTES Received 25 August 2013. Accepted 19 December 2013. Address
correspondence to Alex Bossers, alex.bossers@wur.nl.
Published ahead of print 26 December 2013
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Thursday, December 05, 2013
National Scrapie Eradication Program October 2013 Monthly Report Fiscal
Year 2014 TSE PRION REPORT
Sunday, November 17, 2013
L-BSE in Genetically Susceptible and Resistant Sheep: Changes in Prion
Strain or Phenotypic Plasticity of the Disease-Associated Prion Protein?
Saturday, November 02, 2013
OREGON DETECTS SCRAPIE
Friday, July 26, 2013
Voluntary Scrapie Program USA UPDATE July 26, 2013 increase in FY 2013 is
not statistically meaningful due to the sample size
Greetings BSE-L members et al,
“The increase in FY 2013 is not statistically meaningful due to the sample
size.”
SO, when a TSE mad cow type disease is NOT detectable with a surveillance
system that is set up to test numbers so low you can’t find it, and you complain
on that one factor, then USDA inc tells you that those are the number set up by
OIE inc, and are sufficient to find a TSE mad cow type disease in said species,
and that’s good enough for them, as far as ‘sample size’.
BUT yet, when the shoe is on the other foot so to speak, oh well, it’s a
different story now, the increase in Scrapie cases for the FY 2013 is NOT
meaningful now due to the sample size.
yep, that’s what happened out in the Trans Pecos region where I told the
TAHC et al to test for CWD ten years ago, I complained about that sample size
being totally insufficient, where I knew the CWD positives were waltzing into
Texas, well, they let these CWD positives do it for another 10 years before
doing anything about it, and when they finally increased the sample size, guess
what, they found CWD in TEXAS.
same thing happened with mad cow disease. they increased the sample size,
found it, scared the hell out of them because of all the atypicals, and
immediately shut it down, back to OIE numbers, where you cannot find a TSE prion
disease. what a bunch of hypocrites, and what a joke. all of them.
I suppose the high number of goat cases in California and Michigan, and the
two meat-type twin goats residing in the same herd that tested positive, both
that were submitted as clinical suspects, I guess that’s just another
happenstance of bad luck, another spontaneous event, ...really?
*** I have been trying to bring awareness to the increase in numbers of
goat scrapie cases in certain areas for years now from different potential
sources, to no avail. how many of them might be BSE? as the USDA inc, the OIE
inc, CFIA inc, all try to make typical scrapie a legal trading commodity (they
have already done this with the atypical scrapie, a very foolish move, one that
risk both humans and animals around the globe to the TSE mad cow type agent).
this voluntary scrapie program will not work, in my opinion, the USDA, OIE,
CFIA, know this, so the next best thing is just to force feed all of us around
the globe the TSE prion mad cow type agent by exempting it all $$$ it’s all
gonna catch up sooner or later. just my take. ...
Friday, July 26, 2013
Voluntary Scrapie Program USA UPDATE July 26, 2013 increase in FY 2013 is
not statistically meaningful due to the sample size http://scrapie-usa.blogspot.com/2013/07/voluntary-scrapie-program-usa-update.html
Sunday, June 2, 2013
Characterisation of an Unusual TSE in a Goat by Transmission in Knock-in
Transgenic Mice
Saturday, July 6, 2013
*** Small Ruminant Nor98 Prions Share Biochemical Features with Human
Gerstmann-Sträussler-Scheinker Disease and Variably Protease-Sensitive
Prionopathy
Research Article
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
Wednesday, January 18, 2012
BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE
February 1, 2012
Wednesday, January 18, 2012
Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural
Scrapie Isolates Similar to CH1641 Experimental Scrapie
Journal of Neuropathology & Experimental Neurology:
February 2012 - Volume 71 - Issue 2 - p 140–147
Thursday, July 14, 2011
Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical
Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
SHEEP AND BSE
PERSONAL AND CONFIDENTIAL
SHEEP AND BSE
A. The experimental transmission of BSE to sheep.
Studies have shown that the ''negative'' line NPU flock of Cheviots can be
experimentally infected with BSE by intracerebral (ic) or oral challenge (the
latter being equivalent to 0.5 gram of a pool of four cow brains from animals
confirmed to have BSE).
RB264
BSE - TRANSMISSION STUDIES
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
Saturday, December 3, 2011
Isolation of Prion with BSE Properties from Farmed Goat Volume 17, Number
12—December 2011
Wednesday, February 16, 2011
IN CONFIDENCE SCRAPIE TRANSMISSION TO CHIMPANZEES IN CONFIDENCE
Sunday, December 12, 2010
EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2
December 2010
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
Sunday, February 2, 2014
The Presence of Disease-Associated Prion Protein in Skeletal Muscle of
Cattle Infected with Classical Bovine Spongiform Encephalopathy
NOTE Pathology
TSS
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