Deer Prion Proteins Modulate the Emergence and Adaptation of Chronic Wasting Disease Strains
Deer Prion Proteins Modulate the Emergence and Adaptation of Chronic
Wasting Disease Strains
Camilo Duque Velásquez1, Chiye Kim2, Allen Herbst1, Nathalie Daude3, Maria
Carmen Garza4, Holger Wille4, Judd Aiken1 and Debbie McKenzie2#
+ Author Affiliations Center for Prions and Protein Folding Diseases,
Department of Agriculture Food and Nutritional Sciences1 Department of
Biological Sciences2 Department of Medicine3 Department of Biochemistry4,
University of Alberta, Edmonton, Alberta, Canada
ABSTRACT
Transmission of chronic wasting disease (CWD) between cervids is influenced
by the primary structure of the host cellular prion protein (PrPC). In
white-tailed deer, PRNP alleles encode polymorphisms Q95G96 (wt), Q95S96 (S96)
and H95G96 (H95) that differentially impact CWD progression. We hypothesize that
transmission of CWD prions between deer expressing different allotypes of PrPC
modifies the contagious agent affecting disease spread. To evaluate the
transmission properties of CWD prions derived experimentally from deer of four
PRNP genotypes (wt/wt, S96/wt, H95/wt or H95/S96), transgenic (tg) mice
expressing wt (tg33) or S96 (tg60) alleles were challenged with these prion
agents. Passage of deer CWD into tg33 mice resulted in 100% attack rates, with
H95/S96 CWD having significantly longer incubation periods. Disease signs,
neuropathological and PrP-res profiles in infected tg33 mice were similar
between groups, indicating a prion strain (Wisc-1) common to all CWD inocula was
amplified. In contrast, tg60 mice developed prion disease only when inoculated
with the H95/wt and H95/S96 CWD allotypes. Serial passage in tg60 mice resulted
in adaptation of a novel CWD strain (H95+) with distinct biological properties.
Transmission of first-passage tg60CWD-H95+ isolates into tg33 mice, however,
elicited two prion disease presentations consistent with a mixture of strains
associated with different PrP-res glycotypes. Our data indicates that H95-PRNP
heterozygous deer accumulated two CWD strains, whose emergence was dictated by
PrPC primary structure of the recipient host. These findings suggest CWD
transmission between cervids expressing distinct PrPC molecules results in
generation of novel CWD strains.
IMPORTANCE
CWD prions are contagious among wild and captive cervids in North America
and in Korea. We present data linking the amino acid variant Q95H in
white-tailed deer cellular prion protein (PrPC) to the emergence of a novel CWD
strain (H95+). We show that, upon infection, deer expressing H95-PrPC molecules
accumulated a mixture of CWD strains selectively propagated depending on the
PRNP genotype of the host in which passaged. Our study also demonstrates that
mice expressing the deer S96-PRNP allele, previously shown to be resistant to
various cervid prions, are susceptible to H95+ CWD prions. The potential for
generation of novel strains raises the possibility of an expanded host range for
CWD.
FOOTNOTES
↵# Address correspondence to: debbie.mckenzie@ualberta.ca Copyright © 2015
Duque Velásquez et al.
This is an open-access article distributed under the terms of the Creative
Commons Attribution-Noncommerical-ShareAlike 3.0 Unported license, which permits
unrestricted noncommerical use, distribution, and reproduction in any medium,
provided the original author and source are credited.
snip...
Discussion
Transmission of deer H95/wt and H95/S96 CWD allotypes resulted in the
emergence of
334 a distinct CWD strain (H95+). This novel prion agent was identified
when CWD brain
335 homogenates from deer containing H95-PrP molecules were transmitted
into tg60 mice. Passage
336 of these deer homogenates into tg33, however, resulted in a prion
disease phenotype
337 indistinguishable to that observed following infection with wt/wt and
S96/wt CWD. The ability
338 of H95+ deer CWD to cause clinical prion disease in tg60 mice, which
have been shown to be
339 resistant to other CWD isolates, indicates that a new strain has
emerged (45, 47, 48). Our data
340 shows that passage of CWD (wt/wt pool) through H95/wt and H95/S96 deer
resulted in a
341 mixture of at least two CWD strains, distinguishable based on the
tg-deer-PRNP genotype in
342 which they were propagated.
343
344 All deer CWD samples, upon first passage (P1) into tg33 mice, resulted
in similar disease signs,
345 PrP-res and neuropathological features, suggesting expression of
wt-PrPC favored the
346 propagation of a CWD strain (prion conformer) common to all inocula. We
refer to this agent as
347 “Wisc-1”. Our results suggest “Wisc-1” is similar to CWD-1 described by
Angers et al. (54).
348 The white-tailed deer sample analyzed in the Angers et al. study was a
wt/wt CWD positive
349 isolate from Wisconsin. Whether Wisc-1 and CWD-1 are identical is
difficult to ascertain as the
350 white-tailed deer agents were passaged in different transgenic mice.
The H95+ CWD strain
351 differs from Wisc-1, CWD-1 and CWD-2 strains (54, 55).
17
352
353 We found that inoculation of H95/S96 CWD into tg33 mice resulted in
significantly different
354 incubation periods compared to other CWD allotypes. The absence of
wt-PrPCWD in this
355 inoculum and, thus, the lack of homologous prion conversion likely
contributed to the prolonged
356 incubation period. The presence of more than one prion conformer within
this inoculum may
357 result in competition between agents, leading to propagation
interference and extension of the
358 incubation periods (56-59).
359
360 Incubation periods were not statistically different between tg33 mice
infected with wt/wt,
361 H95/wt or S96/wt CWD. Additionally, all tg33 mice presented the same
prion disease phenotype
362 irrespective of the CWD inocula they received. One possible
interpretation for the phenotypic
363 similarities observed between tg33 mice is the “Wisc-1” conformers have
adaptive advantage in
364 hosts (either in deer or tg mice) expressing wt-PrPC. Differences in
incubation periods between
365 H95/wt and H95/S96 infected tg33 mice suggest that the PrPC sequence in
these deer impacted
366 the proportion of accumulated CWD strains. It has previously been
demonstrated in hamster co367
infection experiments that the ratio of strains in a prion mixture
influences the emergence of the
368 fastest replicating or dominant strain (56, 57, 59).
369
370 The differential susceptibility to prion infection is modulated by PrPC
amino acid variability and
371 the invading prion strain (15, 17, 20, 21, 25, 26, 60). Both natural
and experimental infections
372 support the association of the S96-PrPC with reduced susceptibility and
slower progression of
373 CWD (3, 42-48, 55). Tg60 (S96-PrPC) mice were previously shown to be
resistant to CWD
18
isolates from different cervid 374 species (47, 48). In our study, tg60
mice inoculated with wt/wt and
375 S96/wt did not present with clinical disease after > 700 dpi,
however, mice receiving H95/wt and
376 H95/S96 CWD allotypes developed disease signs and presented consistent
neuropathology and
377 PrP-res glycotypes. Second passage of tg60CWD-H95+ isolates into tg60
mice resulted in
378 reduction of the incubation periods and similar phenotypic
characteristics.
379
380 Allogenic transmission of the first passage tg60CWD-H95+ isolates into
tg33 resulted in mice
381 developing two distinct prion disease phenotypes resembling the
“Wisc-1” and “H95+” prion
382 strains. While some animals presented with hyperactivity and displayed
widespread
383 accumulation of disease associated-PrP in brain as well as high
molecular weight PrP-res, others
384 were lethargic with localized PrPCWD deposits and a distinct PrP-res
glycotype. Transmission of
385 diluted tg60CWD-H95+ inoculum resulted in more mice presenting the
tg60-like phenotype. This
386 suggests the tg60 donor mouse, which preferentially amplified the H95+
strain, contained a
387 persistent Wisc-1 fraction that was amplified upon passage at high dose
(10% Bh) in tg33 mice.
388 Transmission of lower doses of the inoculum, likely altered the
proportion of the two-prion
389 conformers, favoring the propagation of the H95+ strain. A similar
outcome is observed when
390 dilutions of TME were passaged in hamsters, resulting in the isolation
of the Hyper and Drowsy
391 strains (56). Transmission of tg60CWD-H95+ isolates into tg33 mice
indicates that individual
392 tg60 mice accumulated CWD agent mixtures. Although prion transmission
experiments in tg
393 mice do not always recapitulate what is observed in the wild (i.e.,
tg60 mice are resistant to a
394 number of different CWD strains whereas 96S homozygous deer are
naturally infected), natural
19
scrapie and CWD isolates have 395 been shown to contain strain mixtures
that can be differentiated
396 by serial passage in mouse models or by histopathological and
biochemical analyses (54, 61-63).
397
398 Deer with S96-PRNP alleles can be infected with CWD but have extended
preclinical periods
399 suggesting they could shed infectivity over longer periods of time
compared to wt homozygous
400 deer (45, 46, 48). Additionally, in CWD endemic areas, white-tailed
deer with S96-PRNP alleles
401 likely have a fitness advantage compared to the more susceptible deer
genotypes and, as a result,
402 the “resistant” allele may become more abundant in the population (64).
An increase in the S96-
403 PRNP allele frequency could also affect the potential for selection of
CWD strains able to infect
404 resistant genotypes. Likewise, other PRNP alleles associated with
extension of the CWD pre405
clinical phase, such as H95-PRNP, could also be subjected to disease-driven
increase in white406
tailed deer populations. Our transmission data shows that deer expressing
H95-PrP accumulate a
407 CWD strain capable of infecting S96-PRNP genotypes unlike other CWD
agents. An increase in
408 the frequency of H95-PRNP would also increase the likelihood of
emergence of H95+ CWD
409 prions. Our data suggest that white-tailed deer expressing different
PrPC allotypes can
410 accumulate and transmit CWD strain mixtures.
411
412 CWD epizootics involve multiple factors including the contagious nature
of the agent, host413
pathogen interactions, agent “strains” and cervid population genetics. Our
data indicates CWD
414 strain emergence is modulated by amino acid polymorphisms in the cervid
PrP. CWD
415 transmission between hosts with different PRNP genotypes (65) has the
potential to generate and
416 select novel prion conformations. Deer expressing H95-PrPC accumulate
CWD prions with
20
different transmission properties 417 as exemplified by its ability to
infect "resistant" S96-PRNP
418 mice. Finally, our study highlights the importance of characterizing
the diversity of CWD strains
419 and their potential for interspecies transmission, as various mammalian
species are susceptible to
420 experimental CWD infection (66-69). Although several lines of evidence
suggest that humans
421 are resistant to CWD prions (70-73), not all CWD strains have been
tested for their zoonotic
422 potential. Our results demonstrating that H95+ deer CWD have different
transmission properties
423 than CWD prions composed of wt- or S96-PrP suggest the need for
evaluation of the
424 transmissibility of CWD allotypes.
P35
ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A
WISCONSIN STRAIN OF CWD
Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of
Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2
Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary
Research Institute, 4.Center for Prions and Protein Folding Diseases, 5
Department of Biological Sciences, University of Alberta, Edmonton AB, Canada
T6G 2P5
The identification and characterization of prion strains is increasingly
important for the diagnosis and biological definition of these infectious
pathogens. Although well-established in scrapie and, more recently, in BSE,
comparatively little is known about the possibility of prion strains in chronic
wasting disease (CWD), a disease affecting free ranging and captive cervids,
primarily in North America. We have identified prion protein variants in the
white-tailed deer population and demonstrated that Prnp genotype affects the
susceptibility/disease progression of white-tailed deer to CWD agent. The
existence of cervid prion protein variants raises the likelihood of distinct CWD
strains. Small rodent models are a useful means of identifying prion strains. We
intracerebrally inoculated hamsters with brain homogenates and phosphotungstate
concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD
endemic area) and experimentally infected deer of known Prnp genotypes. These
transmission studies resulted in clinical presentation in primary passage of
concentrated CWD prions. Subclinical infection was established with the other
primary passages based on the detection of PrPCWD in the brains of hamsters and
the successful disease transmission upon second passage. Second and third
passage data, when compared to transmission studies using different CWD inocula
(Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin
white-tailed deer population is different than the strain(s) present in elk,
mule-deer and white-tailed deer from the western United States endemic
region.
PPo3-7:
Prion Transmission from Cervids to Humans is Strain-dependent
Qingzhong Kong, Shenghai Huang,*Fusong Chen, Michael Payne, Pierluigi
Gambetti and Liuting Qing Department of Pathology; Case western Reserve
University; Cleveland, OH USA *Current address: Nursing Informatics; Memorial
Sloan-Kettering Cancer Center; New York, NY USA
Key words: CWD, strain, human transmission
Chronic wasting disease (CWD) is a widespread prion disease in cervids
(deer and elk) in North America where significant human exposure to CWD is
likely and zoonotic transmission of CWD is a concern. Current evidence indicates
a strong barrier for transmission of the classical CWD strain to humans with the
PrP-129MM genotype. A few recent reports suggest the presence of two or more CWD
strains. What remain unknown is whether individuals with the PrP-129VV/MV
genotypes are also resistant to the classical CWD strain and whether humans are
resistant to all natural or adapted cervid prion strains. Here we report that a
human prion strain that had adopted the cervid prion protein (PrP) sequence
through passage in cervidized transgenic mice efficiently infected transgenic
mice expressing human PrP, indicating that the species barrier from cervid to
humans is prion strain-dependent and humans can be vulnerable to novel cervid
prion strains. Preliminary results on CWD transmission in transgenic mice
expressing human PrP-129V will also be discussed.
Acknowledgement Supported by NINDS NS052319 and NIA AG14359.
PPo2-27:
Generation of a Novel form of Human PrPSc by Inter-species Transmission of
Cervid Prions
Marcelo A. Barria,1 Glenn C. Telling,2 Pierluigi Gambetti,3 James A.
Mastrianni4 and Claudio Soto1 1Mitchell Center for Alzheimer's disease and
related Brain disorders; Dept of Neurology; University of Texas Houston Medical
School; Houston, TX USA; 2Dept of Microbiology, Immunology & Molecular
Genetics and Neurology; Sanders Brown Center on Aging; University of Kentucky
Medical Center; Lexington, KY USA; 3Institute of Pathology; Case western Reserve
University; Cleveland, OH USA; 4Dept of Neurology; University of Chicago;
Chicago, IL USA
Prion diseases are infectious neurodegenerative disorders affecting humans
and animals that result from the conversion of normal prion protein (PrPC) into
the misfolded and infectious prion (PrPSc). Chronic wasting disease (CWD) of
cervids is a prion disorder of increasing prevalence within the United States
that affects a large population of wild and captive deer and elk. CWD is highly
contagious and its origin, mechanism of transmission and exact prevalence are
currently unclear. The risk of transmission of CWD to humans is unknown.
Defining that risk is of utmost importance, considering that people have been
infected by animal prions, resulting in new fatal diseases. To study the
possibility that human PrPC can be converted into the infectious form by CWD
PrPSc we performed experiments using the Protein Misfolding Cyclic Amplification
(PMCA) technique, which mimic in vitro the process of prion replication. Our
results show that cervid PrPSc can induce the pathological conversion of human
PrPC, but only after the CWD prion strain has been stabilized by successive
passages in vitro or in vivo. Interestingly, this newly generated human PrPSc
exhibits a distinct biochemical pattern that differs from any of the currently
known forms of human PrPSc, indicating that it corresponds to a novel human
prion strain. Our findings suggest that CWD prions have the capability to infect
humans, and that this ability depends on CWD strain adaptation, implying that
the risk for human health progressively increases with the spread of CWD among
cervids.
PPo2-7:
Biochemical and Biophysical Characterization of Different CWD
Isolates
Martin L. Daus and Michael Beekes Robert Koch Institute; Berlin,
Germany
Key words: CWD, strains, FT-IR, AFM
Chronic wasting disease (CWD) is one of three naturally occurring forms of
prion disease. The other two are Creutzfeldt-Jakob disease in humans and scrapie
in sheep. CWD is contagious and affects captive as well as free ranging cervids.
As long as there is no definite answer of whether CWD can breach the species
barrier to humans precautionary measures especially for the protection of
consumers need to be considered. In principle, different strains of CWD may be
associated with different risks of transmission to humans. Sophisticated strain
differentiation as accomplished for other prion diseases has not yet been
established for CWD. However, several different findings indicate that there
exists more than one strain of CWD agent in cervids. We have analysed a set of
CWD isolates from white-tailed deer and could detect at least two biochemically
different forms of disease-associated prion protein PrPTSE. Limited proteolysis
with different concentrations of proteinase K and/or after exposure of PrPTSE to
different pH-values or concentrations of Guanidinium hydrochloride resulted in
distinct isolate-specific digestion patterns. Our CWD isolates were also
examined in protein misfolding cyclic amplification studies. This showed
different conversion activities for those isolates that had displayed
significantly different sensitivities to limited proteolysis by PK in the
biochemical experiments described above. We further applied Fourier transform
infrared spectroscopy in combination with atomic force microscopy. This
confirmed structural differences in the PrPTSE of at least two disinct CWD
isolates. The data presented here substantiate and expand previous reports on
the existence of different CWD strains.
UPDATED DATA ON 2ND CWD STRAIN
Wednesday, September 08, 2010
CWD PRION CONGRESS SEPTEMBER 8-11 2010
PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS
*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***
O18
Zoonotic Potential of CWD Prions
Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1,
Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve
University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy,
3Encore Health Resources, Houston, Texas, USA
*** These results indicate that the CWD prion has the potential to infect
human CNS and peripheral lymphoid tissues and that there might be asymptomatic
human carriers of CWD infection.
==================
***These results indicate that the CWD prion has the potential to infect
human CNS and peripheral lymphoid tissues and that there might be asymptomatic
human carriers of CWD infection.***
==================
P.105: RT-QuIC models trans-species prion transmission
Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover
Prion Research Center; Colorado State University; Fort Collins, CO USA
Conversely, FSE maintained sufficient BSE characteristics to more
efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was
competent for conversion by CWD and fCWD.
***This insinuates that, at the level of protein:protein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.
================
***This insinuates that, at the level of protein:protein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.***
================
PRION2013 CONGRESSIONAL ABSTRACTS CWD
Sunday, August 25, 2013
HD.13: CWD infection in the spleen of humanized transgenic mice
Liuting Qing and Qingzhong Kong
Case Western Reserve University; Cleveland, OH USA
Chronic wasting disease (CWD) is a widespread prion disease in free-ranging
and captive cervid species in North America, and there is evidence suggesting
the existence of multiple CWD strains. The susceptibility of human CNS and
peripheral organs to the various CWD prion strains remains largely unclear.
Current literature suggests that the classical CWD strain is unlikely to infect
human brain, but the potential for peripheral infection by CWD in humans is
unknown. We detected protease-resistant PrpSc in the spleens of a few humanized
transgenic mice that were intracerebrally inoculated with natural CWD isolates,
but PrpSc was not detected in the brains of any of the CWD-inoculated mice.
***Our ongoing bioassays in humanized Tg mice indicate that intracerebral
challenge with such PrpSc-positive humanized mouse spleen already led to prion
disease in most animals. ***These results indicate that the CWD prion may have
the potential to infect human peripheral lymphoid tissues.
Oral.15: Molecular barriers to zoonotic prion transmission: Comparison of
the ability of sheep, cattle and deer prion disease isolates to convert normal
human prion protein to its pathological isoform in a cell-free system
Marcelo A.Barria,1 Aru Balachandran,2 Masanori Morita,3 Tetsuyuki
Kitamoto,4 Rona Barron,5 Jean Manson,5 Richard Kniqht,1 James W. lronside1 and
Mark W. Head1
1National CJD Research and Surveillance Unit; Centre for Clinical Brain
Sciences; School of Clinical Sciences; The University of Edinburgh; Edinburgh,
UK; 2National and OIE Reference Laboratory for Scrapie and CWD; Canadian Food
Inspection Agency; Ottawa Laboratory; Fallowfield. ON Canada; 3Infectious
Pathogen Research Section; Central Research Laboratory; Japan Blood Products
Organization; Kobe, Japan; 4Department of Neurological Science; Tohoku
University Graduate School of Medicine; Sendai. Japan; 5Neurobiology Division;
The Roslin Institute and R(D)SVS; University of Edinburgh; Easter Bush;
Midlothian; Edinburgh, UK
Background. Bovine spongiform encephalopathy (BSE) is a known zoonotic
prion disease, resulting in variant Creurzfeldt- Jakob disease (vCJD) in humans.
In contrast, classical scrapie in sheep is thought to offer little or no danger
to human health. However, a widening range of prion diseases have been
recognized in cattle, sheep and deer. The risks posed by individual animal prion
diseases to human health cannot be determined a priori and are difficult to
assess empirically. The fundamemal event in prion disease pathogenesis is
thought to be the seeded conversion of normal prion protein (PrPC) to its
pathological isoform (PrPSc). Here we report the use of a rapid molecular
conversion assay to test whether brain specimens from different animal prion
diseases are capable of seeding the conversion of human PrPC ro PrPSc.
Material and Methods. Classical BSE (C-type BSE), H-type BSE, L-type BSE,
classical scrapie, atypical scrapie, chronic wasting disease and vCJD brain
homogenates were tested for their ability to seed conversion of human PrPC to
PrPSc in protein misfolding cyclic amplification (PMCA) reactions. Newly formed
human PrPSc was detected by protease digestion and western blotting using the
antibody 3F4.
Results. C-type BSE and vCJD were found to efficiently convert PrPC to
PrPSc. Scrapie failed to convert human PrPC to PrPSc. Of the other animal prion
diseases tested only chronic wasting disease appeared to have the capability ro
convert human PrPC to PrPSc. The results were consistent whether the human PrPC
came from human brain, humanised transgenic mouse brain or from cultured human
cells and the effect was more pronounced for PrPC with methionine at codon 129
compared with that with valine.
Conclusion. Our results show that none of the tested animal prion disease
isolates are as efficient as C-type BSE and vCJD in converting human prion
protein in this in vitro assay. ***However, they also show that there is no
absolute barrier ro conversion of human prion protein in the case of chronic
wasting disease.
PRION2013 CONGRESSIONAL ABSTRACTS CWD
Sunday, August 25, 2013
***Chronic Wasting Disease CWD risk factors, humans, domestic cats, blood,
and mother to offspring transmission
cwd to humans ???
there has been no official documentation of cwd to humans on paper, to
date.
cwd transmission studies on humans are illegal.
cwd transmits freely to the squirrel monkey, but not yet to the macaque,
and the macaque is a bit closer to humans than the squirrel monkey.
still, with cwd freely transmitting to the squirrel monkey, scientist are
very concerned about the cwd to human risk factor, exposure, and potential
iatrogenic transmission there from.
85% of human TSE is sporadic cjd, and each and every one of them are up for
debate as to route and source. I believe that friendly fire (iatrogenic) or the
pass it forward mode of the TSE prion will be a large portion of that. all
iatrogenic cjd is, is sporadic cjd until the iatrogenic event is discovered,
documented, put into the academic and then the public domain, which very seldom
happens due to lack of trace back efforts.
see what the authors said about this casual link with cwd to human with the
case of Jeffrey Schwan 26 year old, and personal communications years ago with
cdc about that case. see where it is stated NO STRONG evidence. so, does this
mean there IS casual evidence ???? “Our conclusion stating that we found no
strong evidence of CWD transmission to humans”
From: Terry S. Singeltary Sr.
Sent: Saturday, November 15, 2014 9:29 PM
To: Terry S. Singeltary Sr.
Subject: THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE R. G. WILL 1984
THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE
R. G. WILL
1984
*** The association between venison eating and risk of CJD shows similar
pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK
OF CJD (p = 0.04). (SEE LINK IN REPORT HERE...TSS) PLUS, THE CDC DID NOT PUT
THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ;
snip...
I urge everyone to watch this video closely...terry
*** you can see video here and interview with Jeff's Mom, and scientist
telling you to test everything and potential risk factors for humans ***
July's Milwaukee Journal Sentinel article did prod state officials to ask
CDC to investigate the cases of the three men who shared wild game feasts. The
two men the CDC is still investigating were 55 and 66 years old. But there's
also Kevin Boss, a Minnesota hunter who ate Barron County venison and died of
CJD at 41. And there's Jeff Schwan, whose Michigan Tech fraternity brothers used
to bring venison sausage back to the frat house. His mother, Terry, says that in
May 2001, Jeff, 26, began complaining about his vision. A friend noticed
misspellings in his e-mail, which was totally unlike him. Jeff began losing
weight. He became irritable and withdrawn. By the end of June, he couldn't
remember the four-digit code to open the garage door or when and how to feed his
parents' cats. At a family gathering in July, he stuck to his parents and
girlfriend, barely talking. "On the night we took him to the hospital, he was
speaking like he was drunk or high and I noticed his pupils were so dilated I
couldn't see the irises," his mother says. By then, Jeff was no longer able to
do even simple things on his computer at work, and "in the hospital, he couldn't
drink enough water." When he died on September 27, 2001, an autopsy confirmed he
had sporadic CJD.
In 2000, Belay looked into three CJD cases reported by The Denver Post, two
hunters who ate meat from animals killed in Wyoming and the daughter of a hunter
who ate venison from a plant that processed Colorado elk. All three died of CJD
before they were 30 years old. The CDC asked the USDA to kill 1,000 deer and elk
in the area where the men hunted. Belay and others reported their findings in
the Archives of Neurology, writing that although "circumstances suggested a link
between the three cases and chronic wasting disease, they could find no 'causal'
link." Which means, says Belay, "not a single one of those 1,000 deer tested
positive for CWD. For all we know, these cases may be CWD. What we have now
doesn't indicate a connection. That's reassuring, but it would be wrong to say
it will never happen."
So far, says NIH researcher Race, the two Wisconsin cases pinpointed by the
newspaper look like spontaneous CJD. "But we don't know how CWD would look in
human brains. It probably would look like some garden-variety sporadic CJD."
What the CDC will do with these cases and four others (three from Colorado and
Schwan from Upper Michigan), Race says, is "sequence the prion protein from
these people, inject it into mice and wait to see what the disease looks like in
their brains. That will take two years."
CJD is so rare in people under age 30, one case in a billion (leaving out
medical mishaps), that four cases under 30 is "very high," says Colorado
neurologist Bosque. "Then, if you add these other two from Wisconsin [cases in
the newspaper], six cases of CJD in people associated with venison is very, very
high." Only now, with Mary Riley, there are at least seven, and possibly eight,
with Steve, her dining companion. "It's not critical mass that matters,"
however, Belay says. "One case would do it for me." The chance that two people
who know each other would both contact CJD, like the two Wisconsin sportsmen, is
so unlikely, experts say, it would happen only once in 140 years.
Given the incubation period for TSEs in humans, it may require another
generation to write the final chapter on CWD in Wisconsin. "Does chronic wasting
disease pass into humans? We'll be able to answer that in 2022," says Race.
Meanwhile, the state has become part of an immense experiment.
*** These results would seem to suggest that CWD does indeed have zoonotic
potential, at least as judged by the compatibility of CWD prions and their human
PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests
that if zoonotic CWD occurred, it would most likely effect those of the PRNP
codon 129-MM genotype and that the PrPres type would be similar to that found in
the most common subtype of sCJD (MM1).***
*** The potential impact of prion diseases on human health was greatly
magnified by the recognition that interspecies transfer of BSE to humans by beef
ingestion resulted in vCJD. While changes in animal feed constituents and
slaughter practices appear to have curtailed vCJD, there is concern that CWD of
free-ranging deer and elk in the U.S. might also cross the species barrier.
Thus, consuming venison could be a source of human prion disease. Whether BSE
and CWD represent interspecies scrapie transfer or are newly arisen prion
diseases is unknown. Therefore, the possibility of transmission of prion disease
through other food animals cannot be ruled out. There is evidence that vCJD can
be transmitted through blood transfusion. There is likely a pool of unknown size
of asymptomatic individuals infected with vCJD, and there may be asymptomatic
individuals infected with the CWD equivalent. These circumstances represent a
potential threat to blood, blood products, and plasma supplies. ***
*** IF CWD is not a risk factor for humans, then I guess the FDA et al
recalled all this CWD tainted elk tenderloin (2009 Exotic Meats USA of San
Antonio, TX) for the welfare and safety of the dead elk. ...tss
Exotic Meats USA Announces Urgent Statewide Recall of Elk Tenderloin
Because It May Contain Meat Derived From An Elk Confirmed To Have Chronic
Wasting Disease
Contact: Exotic Meats USA 1-800-680-4375
FOR IMMEDIATE RELEASE -- February 9, 2009 -- Exotic Meats USA of San
Antonio, TX is initiating a voluntary recall of Elk Tenderloin because it may
contain meat derived from an elk confirmed to have Chronic Wasting Disease
(CWD). The meat with production dates of December 29, 30 and 31, 2008 was
purchased from Sierra Meat Company in Reno, NV. The infected elk came from Elk
Farm LLC in Pine Island, MN and was among animals slaughtered and processed at
USDA facility Noah’s Ark Processors LLC.
Chronic Wasting Disease (CWD) is a fatal brain and nervous system disease
found in elk and deer. The disease is caused by an abnormally shaped protein
called a prion, which can damage the brain and nerves of animals in the deer
family. Currently, it is believed that the prion responsible for causing CWD in
deer and elk is not capable of infecting humans who eat deer or elk contaminated
with the prion, but the observation of animal-to-human transmission of other
prion-mediated diseases, such as bovine spongiform encephalopathy (BSE), has
raised a theoretical concern regarding the transmission of CWD from deer or elk
to humans. At the present time, FDA believes the risk of becoming ill from
eating CWD-positive elk or deer meat is remote. However, FDA strongly advises
consumers to return the product to the place of purchase, rather than disposing
of it themselves, due to environmental concerns.
Exotic Meats USA purchased 1 case of Elk Tenderloins weighing 16.9 lbs. The
Elk Tenderloin was sold from January 16 – 27, 2009. The Elk Tenderloins was
packaged in individual vacuum packs weighing approximately 3 pounds each. A
total of six packs of the Elk Tenderloins were sold to the public at the Exotic
Meats USA retail store. Consumers who still have the Elk Tenderloins should
return the product to Exotic Meats USA at 1003 NE Loop 410, San Antonio, TX
78209. Customers with concerns or questions about the Voluntary Elk Recall can
call 1-800-680-4375. The safety of our customer has always been and always will
be our number one priority.
Exotic Meats USA requests that for those customers who have products with
the production dates in question, do not consume or sell them and return them to
the point of purchase. Customers should return the product to the vendor. The
vendor should return it to the distributor and the distributor should work with
the state to decide upon how best to dispose. If the consumer is disposing of
the product he/she should consult with the local state EPA office.
#
RSS Feed for FDA Recalls Information11 [what's this?12]
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease
Exposure, 2006-2007 FoodNet Population Survey Journal of the American Dietetic
Association Volume 111, Issue 6 , Pages 858-863, June 2011.
now, let’s see what the authors said about this casual link, personal
communications years ago. see where it is stated NO STRONG evidence. so, does
this mean there IS casual evidence ???? “Our conclusion stating that we found no
strong evidence of CWD transmission to humans”
From: TSS (216-119-163-189.ipset45.wt.net)
Subject: CWD aka MAD DEER/ELK TO HUMANS ???
Date: September 30, 2002 at 7:06 am PST
From: "Belay, Ermias"
To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"
Sent: Monday, September 30, 2002 9:22 AM
Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Dear Sir/Madam,
In the Archives of Neurology you quoted (the abstract of which was attached
to your email), we did not say CWD in humans will present like variant CJD. That
assumption would be wrong. I encourage you to read the whole article and call me
if you have questions or need more clarification (phone: 404-639-3091). Also, we
do not claim that "no-one has ever been infected with prion disease from eating
venison." Our conclusion stating that we found no strong evidence of CWD
transmission to humans in the article you quoted or in any other forum is
limited to the patients we investigated.
Ermias Belay, M.D. Centers for Disease Control and Prevention
-----Original Message-----
From: Sent: Sunday, September 29, 2002 10:15 AM
To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS
Thursday, April 03, 2008
A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008
Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.
snip...
*** twenty-seven CJD patients who regularly consumed venison were reported
to the Surveillance Center***,
snip... full text ;
==============================
*** These results would seem to suggest that CWD does indeed have zoonotic
potential, at least as judged by the compatibility of CWD prions and their human
PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests
that if zoonotic CWD occurred, it would most likely effect those of the PRNP
codon 129-MM genotype and that the PrPres type would be similar to that found in
the most common subtype of sCJD (MM1).***
*** The potential impact of prion diseases on human health was greatly
magnified by the recognition that interspecies transfer of BSE to humans by beef
ingestion resulted in vCJD. While changes in animal feed constituents and
slaughter practices appear to have curtailed vCJD, there is concern that CWD of
free-ranging deer and elk in the U.S. might also cross the species barrier.
Thus, consuming venison could be a source of human prion disease. Whether BSE
and CWD represent interspecies scrapie transfer or are newly arisen prion
diseases is unknown. Therefore, the possibility of transmission of prion disease
through other food animals cannot be ruled out. There is evidence that vCJD can
be transmitted through blood transfusion. There is likely a pool of unknown size
of asymptomatic individuals infected with vCJD, and there may be asymptomatic
individuals infected with the CWD equivalent. These circumstances represent a
potential threat to blood, blood products, and plasma supplies.
PRICE OF CWD TSE PRION POKER GOES UP $$$
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Transmission of chronic wasting disease to sentinel reindeer
(Rangifer tarandus tarandus)
Authors
item Moore, S - item Kunkle, Robert item Nicholson, Eric item Richt,
Juergen item Hamir, Amirali item Waters, Wade item Greenlee, Justin
Submitted to: American College of Veterinary Pathologists Meeting
Publication Type: Abstract Only Publication Acceptance Date: August 12, 2015
Publication Date: N/A
Technical Abstract: Chronic wasting disease (CWD) is a naturally-occurring,
fatal neurodegenerative disease of North American cervids. Reindeer (Rangifer
tarandus tarandus) are susceptible to CWD following oral challenge, but CWD has
not been reported in free-ranging caribou (Rangifer tarandus caribou) or farmed
reindeer. Potential contact between CWD-affected cervids and Rangifer species
that are free-ranging or co-housed on farms presents a potential risk of CWD
transmission. The aims of this study were to 1) investigate the transmission of
CWD from white-tailed deer (Odocoileus virginianus; CWD-wtd), mule deer
(Odocoileus hemionus; CWD-md), or elk (Cervus elaphus nelsoni; CWD-elk) to
reindeer via the intracranial route, and 2) to assess for direct and indirect
horizontal transmission to non-inoculated sentinels. Three groups of 5 reindeer
fawns were challenged intracranially with CWD-wtd, CWD-md, or CWD-elk. Two years
after challenge of inoculated reindeer, non-inoculated control reindeer were
introduced into the same pen as the CWD-wtd inoculated reindeer (n=4) or into a
pen adjacent to the CWD-md inoculated reindeer (n=2). Reindeer were allowed to
develop clinical disease. At death/euthanasia a complete necropsy examination
was performed, including immunohistochemical testing of tissues for
disease-associated CWD prion protein (PrP-CWD). Intracranially challenged
reindeer developed clinical disease from 21 months post-inoculation (MPI).
***PrP-CWD was detected in 5/6 sentinel reindeer although only 2/6 developed
clinical disease during the study period (<57 and="" are="" both="" can="" cervid="" cwd="" directly="" div="" from="" have="" indirectly.="" mpi="" naive="" reindeer="" shown="" sources="" susceptible="" that="" to="" transmit="" various="" we="">
***PrP-CWD was detected in 5/6 sentinel reindeer although only 2/6
developed clinical disease during the study period (<57 and="" are="" both="" can="" cervid="" cwd="" directly="" div="" from="" have="" indirectly.="" mpi="" naive="" reindeer="" shown="" sources="" susceptible="" that="" to="" transmit="" various="" we="">
HIGHEST INFECTION RATE ON SEVERAL CWD CONFIRMED CAPTIVES
snip...see more here;
Tuesday, September 29, 2015
*** Transmission of chronic wasting disease to sentinel reindeer (Rangifer
tarandus tarandus) can transmit CWD to naive reindeer both directly and
indirectly
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Friday, August 28, 2015
*** Chronic Wasting Disease CWD TSE Prion Diagnostics and subclinical
infection
Saturday, September 12, 2015
*** In utero transmission and tissue distribution of chronic wasting
disease-associated prions in free-ranging Rocky Mountain elk
>>>Interestingly, five of fifteen sPMCA positive dams showed no
evidence of PrPCWD in either CNS or LRS, sites typically assessed in diagnosing
CWD. Analysis of fetal tissues harvested from the fifteen sPMCA positive dams
revealed PrPCWD in 80% of fetuses (12/15), regardless of gestational stage.
These findings demonstrate that PrPCWD is more abundant in peripheral tissues of
CWD exposed elk than current diagnostic methods suggest, and that transmission
of prions from mother to offspring may contribute to the efficient transmission
of the CWD in naturally exposed cervid populations.<<<
P.141: Abundant prion shedding in CWD-infected deer revealed by Realtime
conversion
Edward A Hoover,1 Davin M Henderson,1 Nathaniel D Denkers,1 Candace K
Mathiason,1 Matteo Manca,2,3 and Byron Caughey2 1Prion Research Center, Colorado
State University; Fort Collins, CO USA; 2Laboratory of Persistent Viral
Diseases, NI AID; Hamilton, MT USA; 3Department of Biomedical Sciences,
University of Cagliari; Monserrato, Italy
Background/Introduction. Chronic wasting disease (CWD) is unique among
prion diseases in its efficient lateral transmission in nature. While the
presence of infectious prions in body fluids and excreta of infected cervids has
been demonstrated by bioassay, the dynamics, magnitude, and consequences of
prion shedding remain unknown. The present studies were undertaken to determine
the kinetics, duration, and magnitude of prion shedding in infected white-tailed
deer.
Materials and Methods. Longitudinal samples were collected from
white-tailed deer over a 2-year span after either oral (n=11)] aerosol (n = 6)
CWD exposure. The assay protocol employed phosphotungstic acid precipitation of
either whole saliva or the pelleted fraction of urine to seed recombinant Syrian
hamster prion PrP substrate in RT-QuIC reactions. Prion seeding activity was
assayed in 8 replicates of each sample employing thioflavin T detection in a
96-well plate-based fluorometer. Prion seeding reaction rate was determined by
taking the inverse of the time at which samples exceeded a threshold of 5
standard deviations above the mean fluorescence of negative controls (1/time to
threshold). Seeding activity was quantitated by comparing the realtime
conversion reaction rate to a standard curve derived from a reference bioassayed
brain pool homogenate from deer with terminal CWD.
Results. We analyzed >200 longitudinally collected, blinded, then
randomized saliva and urine samples from 17 CWDinfected and 3 uninfected
white-tailed deer. We detected prion shedding as early as 3 months post exposure
and sustained thereafter throughout the disease course in both aerosol and
orally exposed deer. The incidence of non-specific false positive results from
> 500 saliva and urine samples from negative control deer was 0.8%. By
comparing real-time reaction rates for these body fluids to a bioassayed
serially diluted brain control, we estimated that ≤1 ml of saliva or urine from
pre-symptomatic infected deer constitutes a lethal infectious prion dose.
Conclusion. CWD prions are shed in saliva and urine of infected deer as
early as 3 months post infection and throughout the subsequent >1.5 year
course of infection. In current work we are examining the relationship of
prionemia to excretion and the impact of excreted prion binding to surfaces and
particulates in the environment.
Acknowledgments. Support: NIH-RO1-NS-061902; Morris Animal Foundation
D12ZO-045
P.154: Urinary shedding of prions in Chronic Wasting Disease infected
white-tailed deer
Nathaniel D Denkers,1 Davin M Henderson, 1 Candace K Mathiason,1 and Edward
A Hoover1 1Prion Research Center, Department of Microbiology, Immunology, and
Pathology, Colorado State University; Fort Collins, CO USA
Background/Introduction. Chronic wasting disease (CWD) is unique among
prion diseases in its efficient lateral transmission in nature, yet the dynamics
and magnitude of shedding and its immediate and long term consequences remain
unknown. The present study was designed to determine the frequency and time span
in which CWD prions are shed in urine from infected white-tailed deer using
adapted real-time quaking-induced conversion (RT-QuIC) methodology.
Materials and Methods. Longitudinal urine samples were collected by free
catch or catheterization over a 2-year period from oral-route infected [CWD+ (n
= 11)] and aerosol-route-infected [CWD+ (n = 6); CWD- (n = 3)] white-tailed
deer. High speed centrifugation pelleted material from 500 µl of urine was
treated with sodium phosphotungstic acid (Na-PTA), resuspended in 0.05% SDS
buffer, and used as seed in RT-QuIC assays employing recombinant Syrian hamster
prion PrP substrate. Eight (8) replicates of each sample were run and prion
seeding activity was recorded as thioflavin T binding fluorescence (480 nm
emission) using a fluorimeter-shaker. Samples were considered positive if they
crossed an established threshold (5 standard deviations above the negative mean
fluorescence).
Results. In our oral-route inoculation studies, prion seeding activity has
been demonstrated in urine collected at 6 months post-inoculation in 6 of 10
deer (11 of 80 replicates; 14%), and intermittently at later time points in all
11 CWD+ exposed deer. Our aerosol-route inoculation studies also showed prion
seeding activity in urine collected at 6 months post-inoculation in 1 of 2 deer
(3 of 16 replicates; 19%), and intermittently at later time points in 4 of 6
CWD+ exposed deer. Urine from sham-inoculated control deer and all baseline
samples yielded 3 false-positive prion seeding activities (3 of 352 replicates;
0.8%).
Conclusion. CWD prions (as inferred by prion seeding activity by RT-QuIC)
are shed in urine of infected deer as early as 6 months post inoculation and
throughout the subsequent disease course. Further studies are in progress
refining the real-time urinary prion assay sensitivity and we are examining more
closely the excretion time frame, magnitude, and sample variables in
relationship to inoculation route and prionemia in naturally and experimentally
CWD-infected cervids.
Acknowledgments. Support: NIH: RO1-NS-061902 and Morris Animal Foundation:
D12ZO-045 P.178: Longitudinal quantitative analysis of CWD prions shed in saliva
of deer
Davin M Henderson, Nina Garbino, Nathaniel D Denkers, Amy V Nalls, Candace
K Mathiason, and Edward A Hoover Prion Research Center, College of Veterinary
Medicine and Biomedical Sciences, Colorado State University; Fort Collins, CO
USA
Background/Introduction. Chronic Wasting Disease (CWD) is an emergent
rapidly spreading fatal prion disease of cervids (deer, elk and moose). CWD has
now been identified in 22 States (including two new states within the last
year), 2 Canadian provinces, and South Korea. Shedding of infectious prions in
excreta (saliva, urine, feces) may be an important factor in CWD transmission.
Here we apply an adapted version of a rapid in vitro assay [real-time
quaking-induced conversion (RT-QuIC)] to determine the time of onset, length,
pattern, and magnitude of prion shedding in saliva of infected deer.
Materials and Methods. The RT-QuIC assay was performed as previously
described in Henderson et al. PLoS-One (2013). Saliva samples were quantitated
by comparison to a RT-QuIC reaction rate standard curve of a bioassayed obex
sample from a terminally ill cervid.
Results. To better understand the onset and length of CWD prion shedding we
analyzed >150 longitudinally collected, blinded, then randomized saliva
samples from 17 CWD-infected and 3 uninfected white-tailed deer. We observed
prion shedding, as detected by the RT-QuIC assay, as early as 3 months from
inoculation and sustained shedding throughout the disease course in both aerosol
and orally exposed deer. We estimated the infectious lethal dose of prions shed
in saliva from infected deer by comparing real-time reaction rates of saliva
samples to a bioassayed serially diluted brain control. Our results indicate
that as little as 1 ml of saliva from pre-symptomatic infected deer constitutes
a lethal CWD prion dose.
Conclusions. During the pre-symptomatic stage of CWD infection and
throughout the course of disease deer may be shedding multiple LD50 doses per
day in their saliva. CWD prion shedding through saliva and excreta may account
for the unprecedented spread of this prion disease in nature.
Acknowledgments. Supported by NIH grant RO1-NS-061902 and grant D12ZO-045
from the Morris Animal Foundation.
Sunday, September 13, 2015
urine, feces, and chronic wasting disease cwd tse prion risk factors,
loading up the environment
Saturday, January 31, 2015
European red deer (Cervus elaphus elaphus) are susceptible to Bovine
Spongiform Encephalopathy BSE by Oral Alimentary route
I strenuously once again urge the FDA and its industry constituents, to
make it MANDATORY that all ruminant feed be banned to all ruminants, and this
should include all cervids as soon as possible for the following
reasons...
======
In the USA, under the Food and Drug Administrations BSE Feed Regulation (21
CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from
deer and elk is prohibited for use in feed for ruminant animals. With regards to
feed for non-ruminant animals, under FDA law, CWD positive deer may not be used
for any animal feed or feed ingredients. For elk and deer considered at high
risk for CWD, the FDA recommends that these animals do not enter the animal feed
system.
***However, this recommendation is guidance and not a requirement by law.
======
31 Jan 2015 at 20:14 GMT
*** Ruminant feed ban for cervids in the United States? ***
31 Jan 2015 at 20:14 GMT
TAHC 393rd Commission Meeting Chronic Wasting Disease CWD TSE Prion October
6, 2015
Saturday, October 03, 2015
TEXAS CHRONIC WASTING DISEASE CWD TSE PRION GOD MUST NOT BE A TEXAN 2002 TO
2015
Friday, August 14, 2015
Susceptibility of cattle to the agent of chronic wasting disease from elk
after intracranial inoculation
Thursday, October 1, 2015
H-type bovine spongiform encephalopathy associated with E211K prion protein
polymorphism: clinical and pathologic features in wild-type and E211K cattle
following intracranial inoculation
Master Obi-Wan Kenobi, Kemosabe...THIS IS NOT GOOD
GOOSE!...grasshopper...tonto...tss
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
12:28 PM
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