Behavior of Prions in the Environment: Implications for Prion Biology
Friday, February 08, 2013
Behavior of Prions in the Environment: Implications for Prion Biology
Behavior of Prions in the Environment: Implications for Prion Biology
•Shannon L. Bartelt-Hunt mail,
* E-mail: sbartelt2@unl.edu (SB); jbartz@creighton.edu (JB) Affiliation:
Department of Civil Engineering, University of Nebraska-Lincoln, Peter Kiewit
Institute, Omaha, Nebraska, United States of America X
•Jason C. Bartz mail
Citation: Bartelt-Hunt SL, Bartz JC (2013) Behavior of Prions in the
Environment: Implications for Prion Biology. PLoS Pathog 9(2): e1003113.
doi:10.1371/journal.ppat.1003113 Editor: Heather True-Krob, Washington
University School of Medicine, United States of America
Published: February 7, 2013
Copyright: © 2013 Bartelt-Hunt, Bartz. 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: This work was supported by the National Science Foundation,
CBET-1149242, (S. Bartelt-Hunt) and the National Center for Research Resources,
P20 RR0115635-6, C06 RR17417-01 and G200RR024001, (J. Bartz). The funders had no
role in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
Competing interests: The authors have declared that no competing interests
exist.
Emergence of Prion Diseases
Prion diseases are infectious, potentially zoonotic neurodegenerative
diseases of animals including humans that are inevitably fatal and are caused by
prions. Prions are comprised of a misfolded isoform of the normal prion protein,
PrPC, into the infectious conformation, PrPSc [1]. Of the known prion diseases,
chronic wasting disease (CWD) of deer, elk, and moose is emerging. CWD was first
identified in captive deer in the front range of Colorado and Wyoming in the
1960s and has since been identified in captive and free-ranging cervids in 20
states, two Canadian provinces, and South Korea (for latest disease distribution
please see http://www.nwhc.usgs.gov/disease_information/chronic_wasting_disease/index.jsp).
While there is evidence of the spread of CWD along known cervid home ranges, the
mechanism underlying the emergence of CWD in geographically isolated areas is
not understood. The prevalence of CWD within an affected population is generally
lower than 5%; however, there are reports of incidence rates that approach 50%.
Transmission of CWD can occur horizontally or through CWD-contaminated
environments, but the relative contribution of each mode in the overall
transmission of CWD is unknown [2]. Since effective control measures are not
available, it is likely that CWD will continue to spread in North America. The
effect of this on the well-being of the cervid population and the risk of
transmission to other species is not known.
Prions Are Released into the Environment and Remain Infectious
It has long been observed that indirect lateral transmission of scrapie can
occur, and recent evidence also demonstrates indirect lateral transmission of
CWD [3]. One factor influencing the environmental transmission of prion diseases
is the long-term survival of prions in the environment. Epidemiological studies
indicate numerous instances of scrapie recurrence upon reintroduction of animals
on farms previously exposed to scrapie. Scrapie recurrence was documented
following fallow periods of 1–16 years [4], and pastures can retain infectious
CWD prions at least 2 years after exposure [5]. Prions are shed from diseased
hosts in a diverse set of biologic matrices, including feces, urine, saliva,
blood, skin, milk, placenta, and nasal mucus. A comprehensive review of prion
shedding was conducted by Gough and Maddison [6]. Prion shedding can occur many
months prior to clinical manifestation of the disease [7]. Prions also enter the
environment after decomposition of diseased animal carcasses [5]. The disposal
of diseased cattle during bovine spongiform encephalopathy (BSE) outbreaks, both
in the past and in potential future disposal events, serves as another
environmental source of prions. Uptake of prions to naïve hosts can occur via
ingestion or inhalation of contaminated material, although the routes of natural
exposure remain uncertain [8]. Recently, scrapie and CWD prions have been
detected in environmental samples by protein misfolding cyclic amplification
(PMCA). One of two water samples collected from a CWD-endemic area in Colorado
was determined to be positive for CWD [9]. Maddison et al. [10] detected scrapie
prions on swabs collected from metal, plastic, and wooden surfaces on a
scrapie-endemic farm. In the Maddison et al. [10] study, it is not clear whether
the scrapie prions associated with the surfaces were co-transported via soil or
dust. To our knowledge, no study has investigated the occurrence of CWD or
scrapie prions in soil samples collected from areas with known incidence of
prion disease.
In the Environment, Prions Can Bind to Soil
Prions shed into the environment will interact with soil. Given the close
contact that animals, especially ruminants, have with soil through routine
behaviors, including ingestion of soil via feeding and mineral supplementation,
there is significant opportunity for transmission of prions via soil. Prions
appear to have an affinity for quartz sands and soils and a particularly strong
affinity for clay minerals [11]. The biological matrix that prions enter the
environment (e.g., urine versus animal carcass) influences the kinetics of prion
sorption to soil. Prions sorb to soil more slowly in complex biological matrices
compared to prions in simple matrices, likely due to competitive interactions
[12]. In addition, the kinetics of PrPSc binding to soil can be influenced by
the prion strain [13]. Sorbed prions are resistant to desorption via detergent
and chaotropic treatments. As with other proteins, prion sorption is most likely
a combination of electrostatic attraction and hydrophobic interactions. Studies
using recombinant prions have identified electrostatic attraction between
positively charged peptides and negatively charged mineral surfaces as the most
significant adsorption mechanisms [14]. Because the N-terminal domain of the
prion protein is known to be flexibly disordered and contains a high number of
positively charged amino acids, it may play a significant role in electrostatic
attraction to negatively charged mineral surfaces. The N-terminal domain is lost
upon desorption of PrPSc from clay, but it is not needed for prion adsorption or
infectivity [11]. Recombinant PrP has a high affinity for organic matter, equal
to or greater than that calculated for mineral surfaces [11]. The
three-dimensional structure of PrPSc remains unknown; therefore, it is a
challenge to model the specific mechanisms that are significant in PrPSc
adsorption to soil. PrPSc is aggregated, and changes in the aggregation state
could occur with soil binding, potentially affecting infectivity. One study did
find that recPrP does not form β-sheets or self-aggregate when adsorbed to clay
[14]. More must be done to determine what conformational changes occur to PrPSc
when it binds to soil or minerals and how these changes affect agent survival
and infectivity.
The Biologic Properties of Prions Can Be Altered by Attachment to Soil
The biologic properties of the prion protein, including conversion activity
and infectivity, can be influenced by attachment to soil particles. Adsorption
of CWD PrPSc to soil reduces prion conversion activity via PMCA [15]. The
observed decrease in the ability of prions to convert upon binding to certain
soils could be due to a number of factors, including conformational changes in
PrPSc structure, interference with PrPC/PrPSc interactions, or a change in PrPSc
stability that may occur upon binding to soil. Several studies have investigated
the role of soil on prion infectivity. Johnson et al. [16] investigated the
infectivity of the hyper strain of transmissible milk encephalopathy (HY TME)
bound to montmorillonite (Mte) clay particles via intracerebral inoculation.
Bioassay results demonstrated a 10-day decrease in incubation period for
PrPSc-Mte complexes when compared to PrPSc inocula without Mte. A second study
investigating infectivity of PrPSc bound to Mte via oral routes also
demonstrated an increase in infectivity relative to clay-free controls [17].
Saunders et al. [15] conducted bioassay experiments using HY TME PrPSc bound to
a silty clay loam soil and demonstrated a 14-day extension in incubation period
and a 1.3 log reduction in titer, as determined by end point dilution, for
soil-bound HY TME prions. This data is consistent with the calculated decrease
in PMCA conversion efficiency for soil-bound HY TME PrPSc. The discrepancies
between observed differences in soil-bound prion infectivity may be explained by
differences in experimental design, such as preparation of PrPSc inocula. Most
importantly, all of these studies consistently demonstrate that prions sorbed to
soil remain highly infectious and that binding to soil can alter prion
infectivity.
The Impact of the Environment on Prion Disease Transmission
The basic parameters of prion environmental interactions are only beginning
to be described, and the effect of these interactions on prion transmission and
pathogenesis are poorly understood. As shown in Figure 1, the interaction of
prions in the environment is complex and must include consideration of the route
of introduction for prions to the environment as well as the effects of soil
properties and prion strain on prion interaction with soil. For example, the
matrix of prion entry into the environment can influence the kinetics of prion
binding to soil. Once bound to soil, prions do not readily disassociate from the
soil particle and remain highly infectious. The implications of these important
observations are that prions immobilized to soil may persist at the surface
where transmission to a naïve host would be more likely to occur. Consistent
with these observations, an increased incidence of CWD corresponds with
geographic regions with soil types that have a high affinity to bind prions
[18]. There is strong evidence for the existence of multiple strains of scrapie,
and recent studies suggest that more than one strain of CWD exists [19].
Strain-specific interactions with the environment may result in preferential
selection of strains that have properties that favor environmental persistence
and transmission.
Figure 1. Factors influencing horizontal transmission of prion disease in
the environment. doi:10.1371/journal.ppat.1003113.g001
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Acknowledgments
We sincerely apologize to our colleagues who we could not cite due to
limitations in the number of references.
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WHAT about the CWD TSE prion in the soil, blowing in the wind to
potentially contaminant land far, far, away ???
Understanding Microbes Blowing in the Wind
By Dennis O'Brien
February 6, 2013
With help from a wind tunnel and the latest DNA technology, U.S.
Department of Agriculture (USDA) scientists are shedding light on the travel
patterns of microbes in soils carried off by strong winds. The work has
implications for soil health and could lead to management practices that
minimize the damage to soils caused by wind erosion.
Wind erosion is an emerging issue in soil conservation efforts.
Agricultural Research Service (ARS) scientists have been studying wind-eroded
soils since the 1930s, but few studies have focused on the effects of wind on
the bacteria, fungi, and protozoa in the soil. ARS is USDA's chief intramural
scientific research agency.
Researchers see an increasing need to focus on pathogens and
agriculturally important bacteria carried in dust. ARS soil scientist Veronica
Acosta-Martinez, with the agency's Wind Erosion and Water Conservation Unit in
Lubbock, Texas, focused on bacterial populations that could be classified by DNA
sequencing. She worked with Terrence Gardner, a visiting scientist from Alabama
A&M University.
Researchers collected airborne dust and samples of a type of organic soil
susceptible to wind erosion from fields where potatoes, beets and onions had
grown a few years earlier and exposed them to windy conditions using a portable
wind tunnel. They characterized the bacteria they found in both the "source
soils" and the wind-eroded sediments, focusing on types of bacteria associated
with coarse particles and on the types associated with fine dust particles.
They classified the bacteria found in each type of soil and wind-eroded
sediment using pyrosequencing, a process that allowed them to identify up to 100
times more DNA in each sample than they would have detected with traditional
methods. The study results, published online in the Journal of Environmental
Quality, showed that certain types of bacteria, known as Bacteroidetes, were
more predominant in the fine dust. Other types, known as Proteobacteria, were
more predominant in coarse sediments.
Studies have shown that Bacteroidetes resist desiccation and thus can
survive in extreme conditions when carried long distances. The fact that
Proteobacteria were associated with coarse eroded sediments, which travel
shorter distances, may explain how soils can retain important qualities despite
damaging winds. Proteobacteria play an important role in carbon and nitrogen
cycling, and their fate in dust storms will be the focus of future research,
according to Acosta-Martinez.
Read more about this research in the February 2013 issue of Agricultural
Research magazine.
2004
Environmental Sources of Prion Transmission in Mule Deer
Michael W. Miller,* Elizabeth S. Williams,† N. Thompson Hobbs,‡ and Lisa
L. Wolfe*
Whether transmission of the chronic wasting disease (CWD) prion among
cervids requires direct interaction with infected animals has been unclear. We
report that CWD can be transmitted to susceptible animals indirectly, from
environments contaminated by excreta or decomposed carcasses. Under experimental
conditions, mule deer (Odocoileus hemionus) became infected in two of three
paddocks containing naturally infected deer, in two of three paddocks where
infected deer carcasses had decomposed in situ ≈1.8 years earlier, and in one of
three paddocks where infected deer had last resided 2.2 years earlier. Indirect
transmission and environmental persistence of infectious prions will complicate
efforts to control CWD and perhaps other animal prion diseases.
2009
Research Article
Infectious Prions in Pre-Clinical Deer and Transmission of Chronic Wasting
Disease Solely by Environmental Exposure
Abstract
Key to understanding the epidemiology and pathogenesis of prion diseases,
including chronic wasting disease (CWD) of cervids, is determining the mode of
transmission from one individual to another. We have previously reported that
saliva and blood from CWD-infected deer contain sufficient infectious prions to
transmit disease upon passage into naïve deer.
Here we again use bioassays in deer to show that blood and saliva of
pre-symptomatic deer contain infectious prions capable of infecting naïve deer
and that naïve deer exposed only to environmental fomites from the suites of
CWD-infected deer acquired CWD infection after a period of 15 months post
initial exposure.
These results help to further explain the basis for the facile
transmission of CWD, highlight the complexities associated with CWD transmission
among cervids in their natural environment, emphasize the potential utility of
blood-based testing to detect pre-clinical CWD infection, and could augur
similar transmission dynamics in other prion infections.
SNIP...
In summary, the results reported here reconfirm that blood and saliva are
sources of infectious CWD prions, consistent with previous findings [27], and
further support a mechanism for efficient CWD transmission in nature. We also
show that infectious prions shed into the environment by CWD+ deer are
sufficient to transmit the disease to naïve deer in the absence of direct
animal-to-animal contact. These observations reinforce the exposure risk
associated with body fluids, excreta, and all tissues from CWD+ cervids and
suggest that similar dynamics may exist in other prion infections.
March 2012
Indirect Environmental Transmission Environmental transmission of the CWD
agent was reported in studies demonstrating that an infected deer carcass left
in a pasture for 2 years could transmit the agent to immunologically naive deer
(17). Exposure of naive deer to pasture previously inhabited by an infected deer
also led to CWD transmission, as did cohabitation of naive and infected deer
(17). Naive deer exposed to water, feed buckets, and bedding used by
CWD-infected deer contracted the disease (18).
Epidemiologic modeling suggests that indirect environmental routes of CWD
transmission also play a major role in transmission (8). Environmental
transmission of scrapie is well documented, and scrapie prions may remain
infectious after years in the environment (19,20; S.E. Saunders, unpub. data).
Nevertheless, environmental transmission of scrapie may be less efficient than
transmission by direct contact (19). Conversely, the relative efficiency of CWD
transmission by direct contact versus indirect, environmental routes remains
unclear, but evidence suggests environmental transmission may be a major
mechanism (8). The proportion of transmission by direct versus indirect routes
may vary not only between captive and free-ranging cervid populations, but also
among cervid species and free-ranging habitats and ecosystems. Transmission
dynamics may also vary over time as CWD prevalence and ecosystem residence times
continue to increase (8).
SEE ;
Salivary prions in sheep and deer
Gültekin Tamgüney,1,2,† Jürgen A. Richt,3,8 Amir N. Hamir,3,9 Justin J.
Greenlee,3 Michael W. Miller,4 Lisa L. Wolfe,4 Tracey M. Sirochman,4 Alan J.
Young,5 David V. Glidden,6 Natrina L. Johnson,1 Kurt Giles,1,2 Stephen J.
DeArmond1,7 and Stanley B. Prusiner1,2,*
1Institute for Neurodegenerative Diseases; San Francisco, CA USA;
2Department of Neurology; University of California, San Francisco, CA USA;
3National Animal Disease Center; ARS-USDA; Ames, IA USA; 4Colorado Division of
Wildlife; Wildlife Research Center; Fort Collins, CO USA; 5Department of
Veterinary Science; South Dakota State University; Brookings, SD USA;
6Departments of Epidemiology and Biostatistics; University of California, San
Francisco, CA USA; 7Department of Pathology; University of California; San
Francisco, CA USA; 8College of Veterinary Medicine; Kansas State University,
Manhattan, KS USA; 9MD Anderson Cancer Center; Houston, TX USA †Current address:
German Center for Neurodegenerative Diseases; Bonn, Germany
Key words: scrapie, chronic wasting disease, saliva, horizontal
transmission, titers
Scrapie of sheep and chronic wasting disease (CWD) of cervids are
transmissible prion diseases. Milk and placenta have been identified as sources
of scrapie prions but do not explain horizontal transmission. In contrast, CWD
prions have been reported in saliva, urine and feces, which are thought to be
responsible for horizontal transmission. While the titers of CWD prions have
been measured in feces, levels in saliva or urine are unknown. Because sheep
produce ~17 L/day of saliva and scrapie prions are present in tongue and
salivary glands of infected sheep, we asked if scrapie prions are shed in
saliva. We inoculated transgenic (Tg) mice expressing ovine prion protein,
Tg(OvPrP) mice, with saliva from seven Cheviot sheep with scrapie. Six of seven
samples transmitted prions to Tg(OvPrP) mice with titers of -0.5 to 1.7 log ID50
U/ml. Similarly, inoculation of saliva samples from two mule deer with CWD
transmitted prions to Tg(ElkPrP) mice with titers of -1.1 to -0.4 log ID50 U/ml.
Assuming similar shedding kinetics for salivary prions as those for fecal prions
of deer, we estimated the secreted salivary prion dose over a 10-mo period to be
as high as 8.4 log ID50 units for sheep and 7.0 log ID50 units for deer. These
estimates are similar to 7.9 log ID50 units of fecal CWD prions for deer.
Because saliva is mostly swallowed, salivary prions may reinfect tissues of the
gastrointestinal tract and contribute to fecal prion shedding. Salivary prions
shed into the environment provide an additional mechanism for horizontal prion
transmission.
Conclusions. This study documents the first aerosol transmission of CWD in
deer. These results further infer that aerosolized prions facilitate CWD
transmission with greater efficiency than does oral exposure to a larger prion
dose. Thus exposure via the respiratory mucosa may be significant in the facile
spread of CWD in deer and perhaps in prion transmission overall.
Conclusion. Transepithelial transport of prions across nasal cavity mucosa
begins within minutes of inhalation and can continue for up to 3 h. While M
cells appear to transport prions across the follicular associated epithelium,
larger amounts of prions are transported between the cells of the respiratory
and olfactory epithelia, where they immediately enter the lymphatic vessels in
the lamina propria. Thus, inhaled prions can be spread via lymph draining the
nasal cavity and have access to somatic and autonomic nerves in the lamina
propria of the nasal cavity. The increased efficiency of the nasal cavity route
of infection compared with the oral route may be due to the rapid and prolonged
transport of prions between cells of the respiratory and olfactory epithelia.
Now that these experiments are completed we conclude that TSE infectivity
is likely to survive burial for long periods of time with minimal loss of
infectivity and restricted movement from the site of burial. These experiments
emphasize that the environment is a viable reservoir for retaining large
quantities of TSE infectivity, and reinforce the importance of risk assessment
when disposing of this type of infectious material.
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced
into Great Britain? A Qualitative Risk Assessment October 2012
Monday, September 17, 2012
Rapid Transepithelial Transport of Prions Following Inhalation
Monday, November 26, 2012
Aerosol Transmission of Chronic Wasting Disease in White-tailed Deer
Monday, November 26, 2012
Rapid Transepithelial Transport of Prions following Inhalation
Enzymatic Digestion of Chronic Wasting Disease Prions Bound to Soil
S A M U E L E . S A U N D E R S , † J A S O N C . B A R T Z , ‡ K U R T C .
V E R C A U T E R E N , § A N D S H A N N O N L . B A R T E L T - H U N T * , †
Department of Civil Engineering, Peter Kiewit Institute, University of
NebraskasLincoln, Omaha, Nebraska 68588, Department of Medical Microbiology and
Immunology, Creighton University, Omaha, Nebraska 68178, and USDA Animal and
Plant Health Inspection Service, Wildlife Services, National Wildlife Research
Center, Fort Collins, Colorado 80521 Received November 19, 2009. Revised
manuscript received April 5, 2010. Accepted April 24, 2010.
Chronic wasting disease (CWD) and sheep scrapie can be transmitted via
indirect environmental routes, and it is known that soil can serve as a
reservoir of prion infectivity. Given the strong interaction between the prion
protein (PrP) and soil, we hypothesized that binding to soil enhances prion
resistance to enzymatic digestion, thereby facilitating prion longevity in the
environment and providing protection from host degradation. We characterized the
performance of a commercially available subtilisin enzyme, Prionzyme, to degrade
soil-bound and unbound CWD and HY TME PrP as a function of pH, temperature, and
treatment time. The subtilisinenzymeeffectively degraded PrP adsorbed to a wide
range of soils and soil minerals below the limits of detection. Signal loss
occurred rapidly at high pH (12.5) and within 7 days under conditions
representative of the natural environment (pH 7.4, 22 °C). We observednoapparent
difference inenzymeeffectivenessbetween bound and unbound CWD PrP. Our results
show that although adsorbed prions do retain relative resistance to enzymatic
digestion compared with other brain homogenate proteins, they can be effectively
degraded when bound to soil. Our results also suggest a topical application of a
subtilisin enzyme solution may be an effective decontamination method to limit
disease transmission via environmental “hot spots” of prion infectivity. see
full text study here ;
CWD TSE prion disease survives ashing to 600 degrees celsius, that’s around
1112 degrees farenheit.
you cannot cook the CWD TSE prion disease out of meat.
you can take the ash and mix it with saline and inject that ash into a
mouse, and the mouse will go down with TSE.
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel
Production as well.
the TSE prion agent also survives Simulated Wastewater Treatment Processes.
IN fact, you should also know that the CWD TSE Prion agent will survive in
the environment for years, if not decades.
you can bury it and it will not go away.
CWD TSE agent is capable of infected your water table i.e. Detection of
protease-resistant cervid prion protein in water from a CWD-endemic area.
it’s not your ordinary pathogen you can just cook it out and be done with.
that’s what’s so worrisome about Iatrogenic mode of transmission, a simple
autoclave will not kill this TSE prion agent.
New studies on the heat resistance of hamster-adapted scrapie agent:
Threshold survival after ashing at 600°C suggests an inorganic template of
replication
Paul Brown*,dagger , Edward H. RauDagger , Bruce K. Johnson*, Alfred E.
Bacote*, Clarence J. Gibbs Jr.*, and D. Carleton Gajdusek§ * Laboratory of
Central Nervous System Studies, National Institute of Neurological Disorders and
Stroke, and Dagger Environmental Protection Branch, Division of Safety, Office
of Research Services, National Institutes of Health, Bethesda, MD 20892; and §
Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198 Gif
sur Yvette, France Contributed by D. Carleton Gajdusek, December 22, 1999
see full text:
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel
Production
Cathrin E. Bruederle,1* Robert M. Hnasko,1 Thomas Kraemer,2 Rafael A.
Garcia,3 Michael J. Haas,3 William N. Marmer,3 and John Mark Carter1 1USDA-ARS
WRRC, Foodborne Contaminants Research Unit, Albany, California, United States of
America 2Forensic Toxicology, Institute of Legal Medicine, Saarland University,
Homburg/Saar, Germany 3USDA-ARS ERRC, Fats, Oils and Animal Coproducts Research
Unit, Wyndmoor, Pennsylvania, United States of America Neil Mabbott,
EditorUniversity of Edinburgh, United Kingdom *
Wednesday, October 14, 2009
Detection of protease-resistant cervid prion protein in water from a
CWD-endemic area
T.A. Nichols,1,2 Bruce Pulford,1 A. Christy Wyckoff,1,2 Crystal Meyerett,1
Brady Michel,1 Kevin Gertig,3 Edward A. Hoover,1 Jean E. Jewell,4 Glenn C.
Telling5 and Mark D. Zabel1,*
1Department of Microbiology, Immunology and Pathology; College of
Veterinary Medicine and Biomedical Sciences; Colorado State University; Fort
Collins, CO USA; 2National Wildlife Research Center; Wildlife Services; United
States Department of Agriculture; Fort Collins, CO USA; 3Fort Collins Utilities;
Fort Collins; CO USA; 4Department of Veterinary Sciences; Wyoming State
Veterinary Laboratory; University of Wyoming; Laramie, WY USA; 5Department of
Microbiology, Immunology, Molecular Genetics and Neurology; Sanders Brown Center
on Aging; University of Kentucky; Lexington, KY USA
snip...
The data presented here demonstrate that sPMCA can detect low levels of
PrPCWD in the environment, corroborate previous biological and experimental data
suggesting long term persistence of prions in the environment2,3 and imply that
PrPCWD accumulation over time may contribute to transmission of CWD in areas
where it has been endemic for decades. This work demonstrates the utility of
sPMCA to evaluate other environmental water sources for PrPCWD, including
smaller bodies of water such as vernal pools and wallows, where large numbers of
cervids congregate and into which prions from infected animals may be shed and
concentrated to infectious levels.
snip...see more here ;
Monday, August 8, 2011
Susceptibility of Domestic Cats to CWD Infection
Oral.29: Susceptibility of Domestic Cats to CWD Infection
for those interested, you can see the program here ;
PRION 2011
PrioNet Canada and the Alberta Prion Research Institute are proud to
co-host the world’s largest international prion research conference, PRION 2011,
in Montreal, Quebec from May 16-19. This is the first time this conference is
being presented outside of Europe. This international PRION 2011 congress will
follow in the same tradition as past PRION conferences and aims to welcome over
600 attendees from around the world. PRION 2011 anticipates over 55 speakers and
will include an outstanding list of plenary lectures, special sessions, “hot
topic” panels, networking activities, and poster presentations.
Prion diseases know no borders, and this congress represents the one annual
event to bring together experts from around the world to discuss a broad
spectrum of topics, from surveillance and control, to prion structure and
function, to diagnostics and therapeutics, ultimately with the goal to enhance
the pace of prion research to mitigate the negative impacts of prion disease on
society. This meeting will also cover the new connections between prion diseases
and other human misfolding protein diseases such as Alzheimer’s, Parkinson’s and
others. Prion-like propagation of protein misfolding will be one of four special
themes of the meeting.
We look forward to your participation!
The PRION 2011 Steering Committee
Thursday, February 17, 2011
Environmental Sources of Scrapie Prions
Saturday, May 14, 2011
Modeling Routes of Chronic Wasting Disease Transmission: Environmental
Prion Persistence Promotes Deer Population Decline and Extinction
Tuesday, December 18, 2012
A Growing Threat How deer breeding could put public trust wildlife at risk
Friday, November 09, 2012
Chronic Wasting Disease CWD in cervidae and transmission to other species
Sunday, November 11, 2012
Susceptibilities of Nonhuman Primates to Chronic Wasting Disease November
2012
Friday, December 14, 2012
Susceptibility Chronic Wasting Disease (CWD) in wild cervids to Humans 2005
- December 14, 2012
PRION 2010
International Prion Congress: From agent to disease September 8–11, 2010
Salzburg, Austria
PRION 2010 is the top Global Annual TSE Conference in prion research,
following a sequence of PRION meetings that were originally organized by the EU
Network of Excellence NeuroPrion. In this proud tradition, PRION 2010 covers all
aspects of this fascinating scientific area. PRION 2010 is a meeting of greatest
interest for neuroscientists, protein structural biologists, geneticists,
medical specialists including neurologists, neuropathologists, hygiene experts
and blood product providers, veterinarians, epidemiologists, laboratory
technicians, industry developers, risk assessors and managers. An outstanding
list of Plenary Lecture, Symposia and Workshop Speakers is complemented by the
plethora of original input from Poster Presentations. Special consideration is
given this year to two areas of major interest: the renewed discussion about the
zoonotic potential of animal prion diseases, given the emergence of atypical BSE
and scrapie strains, and the breakthrough work on synthetic prions by several
groups simultaneously.
snip...
PPo4-4:
Survival and Limited Spread of TSE Infectivity after Burial
Karen Fernie, Allister Smith and Robert A. Somerville The Roslin Institute
and R(D)SVS; University of Edinburgh; Roslin, Scotland UK
The authors gratefully acknowledge funding from DEFRA.
PPo8-14:
Enzymatic Digestion of Chronic Wasting Disease Prions Bound to Soil
Samuel E. Saunders,1 Jason C. Bartz,2 Kurt C. Vercauteren3 and Shannon L.
Bartelt-Hunt1 1Department of Civil Engineering; University of Nebraska-Lincoln;
Peter Kiewit Institute; Omaha, Nebraska USA; 2Department of Medical Microbiology
and Immunology; Creighton University; Omaha, Nebraska USA; 3USDA; Animal and
Plant Health Inspection Service; Wildlife Services; National Wildlife Research
Center; Fort Collins, CO USA
Chronic wasting disease (CWD) and sheep scrapie can be transmitted via
indirect environmental routes, and it is known that soil can serve as a
reservoir of prion infectivity. Given the strong interaction between the prion
protein (PrP) and soil, we hypothesized that binding to soil enhances prion
resistance to enzymatic digestion, thereby facilitating prion longevity in the
environment and providing protection from host degradation. We characterized the
performance of a commercially available subtilisin enzyme, the Prionzyme, to
degrade soil-bound and unbound CWD and HY TME PrP as a function of pH,
temperature, and treatment time. The subtilisin enzyme effectively degraded PrP
adsorbed to a wide range of soils and soil minerals below the limits of
detection. Signal loss occurred rapidly at high pH (12.5) and within 7 d under
conditions representative of the natural environment (pH 7.4, 22°C). Serial PMCA
of treated soil samples suggests a greater than 6-log decrease in infectious
titer compared with controls. We observed no apparent difference in enzyme
effectiveness between bound and unbound CWD PrP. Our results show that although
adsorbed prions do retain relative resistance to enzymatic digestion compared
with other brain homogenate proteins, they can be effectively degraded when
bound to soil. Our results also suggest a topical application of a subtilisin
enzyme solution may be an effective decontamination method to limit disease
transmission via environmental ‘hot spots’ of prion infectivity.
PPo8-13:
Degradation of Pathogenic Prion Protein and Prion Infectivity by Lichens
Christopher J. Johnson,1 James P. Bennett,1 Steven M. Biro,1,2 Cynthia M.
Rodriguez,1,2 Richard A. Bessen3 and Tonie E. Rocke1
1USGS National Wildlife Health Center; 2Department of Bacteriology;
University of Wisconsin, Madison; 3Department of Veterinary Molecular Biology;
Montana State University; Bozeman, MT USA
Key words: prion, lichen, bioassay, protease, degradation
Few biological systems have been identified that degrade the transmissible
spongiform encephalopathy (TSE)-associated form of the prion protein (PrPTSE)
and TSE infectivity. Stability of the TSE agent allows scrapie and chronic
wasting disease agents to persist in the environment and cause disease for
years. Naturally-occurring or engineered processes that reduce infectivity in
the environment could aid in limiting environmental TSE transmission. We have
previously identified that species of at least three lichens, unusual, symbiotic
organisms formed from a fungus and photosynthetic partner, contain a serine
protease capable of degrading PrPTSE under gentle conditions. We tested the
hypothesis that lichen extracts from these three species reduce TSE infectivity
by treating infected brain homogenate with extracts and examining infectivity in
mice. We found lichen extracts diminished TSE infectious titer by factors of 100
to 1,000 and that reductions in infectivity were not well-correlated with the
extent of PrPTSE degradation observed by immunoblotting. For example, treatment
of brain homogenate with Cladonia rangiferina extract caused <100-fold activity="" after="" agents.="" also="" and="" anti-prion="" but="" characterization="" cladonia="" closely="" clusters="" comparison="" data="" decrease="" degradation="" degrade="" div="" do="" extract="" favors="" focus="" fold="" for="" forms="" genera="" has="" immunoreactivity="" in="" indicate="" infectious="" infectivity="" known="" lichen="" more="" necessarily="" not="" of="" on="" or="" our="" phylogeny="" prion-degrading="" protease="" prp="" prptse.="" prptse="" reduction="" related="" remaining="" rendered="" searches="" some="" species-specificity="" species="" suggesting="" that="" the="" those="" to="" treatment="" uninfectious="" usnea="" was="" which="" with="" within="" yielded="">
PPo8-20:
The Anti-prion Activity of Soil Organic Compounds Humic and Fulvic Acids
Joanna Narkiewicz,1,2 Ai H.N. Tran,1 Gabriele Giachin,1 Liviana Leita2 and
Giuseppe Legname1, 1Neurobiology Sector; Scuola Internazionale Superiore di
Studi Avanzati; International School for Advanced Studies; Bonomea, Trieste
Italy; 2Agricultural Research Council (CRA); Research Centre for Soil-Plant
System; Trieste, Gorizia Italy
A notable feature of prion diseases, as scrapie in sheep and chronic
wasting disease in mule deer and elk, is horizontal transmission between grazing
animals, suggesting that contaminated environment may contribute significantly
to disease transmission. Increasing evidence suggests that soil may present
natural reservoir of prion infectivity. Recent studies have shown that prions
may persist in contaminated soil and remain infectious for years. As the
mechanism of prion retention and persistence in soil is unknown, it is necessary
to understand which soil components may interact with prions and thus contribute
to disease transmission. Several reports indicate that prion have potential to
interact with soil minerals, however the contribution of soil organic fraction
in adsorption to prions has been neglected. Here, we present strong evidence for
soil humic substances (HS) interaction with prions. We show that two HS,
classified as humic and fulvic acids, interact with recombinant prion proteins
in vitro. Moreover, we show that both HS possess anti-prion activity, both in
vivo and in vitro. Both compounds induced elimination of PrPSc from chronically
scrapie-infected GT1 mouse hypothalamic cells (ScGT1) in a dose-dependent
manner. ScGT1 cells treatment with HS at concentration of 20mg/mL eliminated
more than 95% of PrPSc and did not affect cell viability. Moreover, both HS
induced inhibition of prion fibril formation in vitro, as determined by
thioflavin T assay. Our results suggest that HS may contribute significantly to
prion inactivation in natural soil environments.
PPo8-21:
Detection of PrPCWD in Rocky Mountain Elk Feces Using Protein Misfolding
Cyclic Amplification
Bruce E Pulford,1 Terry Spraker,1 Jenny Powers,2 Margaret Wild2 and Mark
D. Zabel1 1Department of Microbiology; Immunology and Pathology; College of
Veterinary Medicine and Biomedical Sciences; Colorado State University;
2Biological Resource Management Division; United States National Park Service;
CO, USA
Key words: CWD, feces, PMCA, elk
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy
affecting cervids, including mule and white-tailed deer (Odocoileus hemionus and
virginianus), elk (Cervus elaphus nelsoni) and moose (Alces alces shirasi). The
method of CWD transmission between hosts is unclear, though there is evidence
that feces excreted by infected animals may play a role. Recently, CWD prions
was detected in feces using bioassays in cervidized mice, which took many months
to produce results. In this study, we use a more rapid procedure, protein
misfolding cyclic amplification (PMCA), to test elk feces for the presence of
PK-resistant cervid PrP (PrPCWD). Feces were collected from symptomatic and
asymptomatic elk in several northern Colorado locations, homogenized, mixed with
normal brain homogenate from Tg5037 mice (expressing cervid PrP) and subjected
to up to 9 rounds of PMCA (1 round = 40 secs sonication/30 mins at 70% maximum
power, 24 hours). Western blots were used to detect PrPCWD using BAR-224
anti-PrP antibody. Rectal and CNS tissue from the elk were IHC-labeled and
examined for the presence of PrPCWD. Fecal samples from symptomatic and
asymptomatic elk that tested positive by IHC showed characteristic PrPCWD bands
on western blots following PMCA. In addition, PMCA detected PrPCWD in 25% of
fecal samples from IHC-negative animals. These data suggest that PMCA may (1)
prove useful as a non-invasive method to supplement or even replace IHC testing
of cervids for CWD, and (2) identify additional asymptomatic carriers of CWD,
the prevalence of which may be underestimated using IHC.
see full text and more ;
Friday, February 25, 2011
Soil clay content underlies prion infection odds
UPDATED DATA ON 2ND CWD STRAIN
Wednesday, September 08, 2010
CWD PRION CONGRESS SEPTEMBER 8-11 2010
tss
posted by Terry S. Singeltary Sr. at
1:47 PM
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