Rapid Transepithelial Transport of Prions following Inhalation
Rapid Transepithelial Transport of Prions following Inhalation
Anthony E. Kincaida,b,c, Kathryn F. Hudsona,*, Matthew W. Richeya and Jason
C. Bartzc
+ Author Affiliations
aDepartment of Physical Therapy
bDepartment of Biomedical Sciences
cDepartment of Medical Microbiology and Immunology, Creighton University,
Omaha, Nebraska, USA
ABSTRACT
Prion infection and pathogenesis are dependent on the agent crossing an
epithelial barrier to gain access to the recipient nervous system. Several
routes of infection have been identified, but the mechanism(s) and timing of in
vivo prion transport across an epithelium have not been determined. The hamster
model of nasal cavity infection was used to determine the temporal and spatial
parameters of prion-infected brain homogenate uptake following inhalation and to
test the hypothesis that prions cross the nasal mucosa via M cells. A small drop
of infected or uninfected brain homogenate was placed below each nostril, where
it was immediately inhaled into the nasal cavity. Regularly spaced tissue
sections through the entire extent of the nasal cavity were processed
immunohistochemically to identify brain homogenate and the disease-associated
isoform of the prion protein (PrPd). Infected or uninfected brain homogenate was
identified adhering to M cells, passing between cells of the nasal mucosa, and
within lymphatic vessels of the nasal cavity at all time points examined. PrPd
was identified within a limited number of M cells 15 to 180 min following
inoculation, but not in the adjacent nasal mucosa-associated lymphoid tissue
(NALT). While these results support M cell transport of prions, larger amounts
of infected brain homogenate were transported paracellularly across the
respiratory, olfactory, and follicle-associated epithelia of the nasal cavity.
These results indicate that prions can immediately cross the nasal mucosa via
multiple routes and quickly enter lymphatics, where they can spread systemically
via lymph draining the nasal cavity.
FOOTNOTES Received 24 July 2012. Accepted 5 September 2012. Address
correspondence to Anthony E. Kincaid, akincaid@creighton.edu.
↵* Present address: Kathryn F. Hudson, Department of Pharmacology, Emory
University, Atlanta, Georgia, USA.
Published ahead of print 12 September 2012
Copyright © 2012, American Society for Microbiology. All Rights Reserved.
Monday, November 26, 2012
Aerosol Transmission of Chronic Wasting Disease in White-tailed Deer
Nathaniel D. Denkers1, Jeanette Hayes-Klug1, Kelly R. Anderson1, Davis M.
Seelig1, Nicholas J. Haley1, Sallie J. Dahmes2, David A. Osborn3, Karl V.
Miller3, Robert J. Warren3, Candace K. Mathiason1 and Edward A. Hoover1,* +
Author Affiliations 1 Department of Microbiology, Immunology, and Pathology,
Colorado State University, Fort Collins, CO 80523-1619 2WASCO Inc., Monroe,
Georgia 3Warnell School of Forestry and Natural Resources, University of
Georgia, Athens, Georgia
ABSTRACT
While the facile transmission of chronic wasting disease (CWD) remains
incompletely elucidated, studies in rodents suggest exposure of the respiratory
mucosa may be an efficient pathway. The present study was designed to address
this question in the native cervid host. Here we demonstrate aerosol
transmission of CWD to deer with a prion dose >20-fold lower than that used
in previous oral inoculations. Inhalation of prions may facilitate transmission
of CWD and perhaps other prions infections.
FOOTNOTES ↵*Correspondence: Edward A. Hoover, Department of Microbiology,
Immunology, and Pathology, Campus Delivery 1619, Colorado State University, Fort
Collins, CO 80523-1619, Phone: 970-491-7587, Fax: 970-491-0523,
edward.hoover@colostate.edu Copyright © 2012, American Society for Microbiology.
All Rights Reserved.
Thursday, May 31, 2012
CHRONIC WASTING DISEASE CWD PRION2012 Aerosol, Inhalation transmission,
Scrapie, cats, species barrier, burial, and more
Thursday, December 29, 2011
Aerosols An underestimated vehicle for transmission of prion diseases?
PRION www.landesbioscience.com
please see more on Aerosols and TSE prion disease here ;
Elk and Deer Use of Mineral Licks: Implications for Disease Transmission
Kurt C. VerCauteren1*, Michael J. Lavelle1, Gregory E. Phillips1, Justin W.
Fischer1, and Randal S. Stahl1 1United States Department of Agriculture, Animal
and Plant Health Inspection Service, Wildlife Services, National Wildlife
Research Center, 4101 LaPorte Avenue, Fort Collins, CO 80521-2154, USA
*Cooresponding author e-mail: kurt.c.vercauteren@aphis.usda.gov North American
cervids require and actively seek out minerals to satisfy physiological
requirements. Minerals required by free-ranging cervids exist within natural and
artificial mineral licks that commonly serve as focal sites for cervids.
Ingestion of soils contaminated with the agent that causes chronic wasting
disease (CWD) may result in risk of contracting CWD. Our objective was to
evaluate the extent and nature of use of mineral licks by CWD-susceptible cervid
species. We used animal-activated cameras to monitor use of 18 mineral licks
between 1 June and 16 October 2006 in Rocky Mountain National Park,
north-central Colorado. We also assessed mineral concentrations at mineral licks
to evaluate correlations between visitation rates and site-specific
characteristics. We collected > 400,000 images of which 991 included elk, 293
included deer, and 6 included moose. We documented elk and deer participating in
a variety of potentially risky behaviors (e.g., ingesting soil, ingesting water,
defecating, urinating) while at mineral licks. Results from the mineral analyses
combined with camera data revealed that visitation was highest at sodium-rich
mineral licks. Mineral licks may play a role in disease transmission by acting
as sites of increased interaction as well as reservoirs for deposition,
accumulation, and ingestion of disease agents.
In conclusion, aerosols can infect mice with a surprisingly high
efficiency. Just how important a role is played by this newly recognized pathway
of spread in natural transmission is, as of now, unclear and in need of further
studies. Although it was not identified as a route of infection in
epidemiological studies thus far, the worryingly high attack rate suggests that
we would be well-advised to carefully avoid the inhalation of aerosols from
prion-containing materials. Key words: prion, prion transmission, scrapie,
chronic wasting diseases, CWD, Creutzfeldt-Jacob-disease, CJD, TSE, aerosol,
pathogens, allergens Submitted: 05/19/11 Accepted: 06/09/11 DOI:
10.4161/pri.5.3.16851 *Correspondence to: Lothar Stitz or Adriano Aguzzi; Email:
lothar.stitz@fli.bund.de or adriano.aguzzi@usz.ch
PLEASE SEE FULL TEXT, AND AGAIN, many thanks to PLOS for open access !!!
Monday, September 17, 2012
Rapid Transepithelial Transport of Prions Following Inhalation
CWD has been identified in free-ranging cervids in 15 US states and 2
Canadian provinces and in ≈ 100 captive herds in 15 states and provinces and in
South Korea (Figure 1, panel B). SNIP... Long-term effects of CWD on cervid
populations and ecosystems remain unclear as the disease continues to spread and
prevalence increases. In captive herds, CWD might persist at high levels and
lead to complete herd destruction in the absence of human culling. Epidemiologic
modeling suggests the disease could have severe effects on free-ranging deer
populations, depending on hunting policies and environmental persistence (8,9).
CWD has been associated with large decreases in free-ranging mule deer
populations in an area of high CWD prevalence (Boulder, Colorado, USA) (5).
PLEASE STUDY THIS MAP, COMPARE FARMED CWD TO WILD CWD...TSS
Saturday, February 18, 2012
Occurrence, Transmission, and Zoonotic Potential of Chronic Wasting Disease
CDC Volume 18, Number 3—March 2012
CWD has been identified in free-ranging cervids in 15 US states and 2
Canadian provinces and in ≈100 captive herds in 15 states and provinces and in
South Korea (Figure 1, panel B).
Subject: CWD TSE PRION, AND SCRAPIE ?
*** Spraker suggested an interesting explanation for the occurrence of CWD.
The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr.
Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at
this site. When deer were introduced to the pens they occupied ground that had
previously been occupied by sheep.
White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection
Jodi D. Smith, Justin J. Greenlee, and Robert A. Kunkle; Virus and Prion
Research Unit, National Animal Disease Center, USDA-ARS
Interspecies transmission studies afford the opportunity to better
understand the potential host range and origins of prion diseases. Previous
experiments demonstrated that white-tailed deer are susceptible to sheep-derived
scrapie by intracranial inoculation. The purpose of this study was to determine
susceptibility of white-tailed deer to scrapie after a natural route of
exposure. Deer (n=5) were inoculated by concurrent oral (30 ml) and intranasal
(1 ml) instillation of a 10% (wt/vol) brain homogenate derived from a sheep
clinically affected with scrapie. Non-inoculated deer were maintained as
negative controls. All deer were observed daily for clinical signs. Deer were
euthanized and necropsied when neurologic disease was evident, and tissues were
examined for abnormal prion protein (PrPSc) by immunohistochemistry (IHC) and
western blot (WB). One animal was euthanized 15 months post-inoculation (MPI)
due to an injury. At that time, examination of obex and lymphoid tissues by IHC
was positive, but WB of obex and colliculus were negative. Remaining deer
developed clinical signs of wasting and mental depression and were necropsied
from 28 to 33 MPI. Tissues from these deer were positive for scrapie by IHC and
WB. Tissues with PrPSc immunoreactivity included brain, tonsil, retropharyngeal
and mesenteric lymph nodes, hemal node, Peyer’s patches, and spleen. This work
demonstrates for the first time that white-tailed deer are susceptible to sheep
scrapie by potential natural routes of inoculation. In-depth analysis of tissues
will be done to determine similarities between scrapie in deer after
intracranial and oral/intranasal inoculation and chronic wasting disease
resulting from similar routes of inoculation.
see full text ;
PO-039:
A comparison of scrapie and chronic wasting disease in white-tailed deer
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture;
Agricultural Research Service, National Animal Disease Center; Ames, IA USA
White-tailed deer are susceptible to the agent of sheep scrapie by
intracerebral inoculation snip... It is unlikely that CWD will be eradicated
from free-ranging cervids, and the disease is likely to continue to spread
geographically [10]. However, the potential that white-tailed deer may be
susceptible to sheep scrapie by a natural route presents an additional
confounding factor to halting the spread of CWD. This leads to the additional
speculations that 1) infected deer could serve as a reservoir to infect sheep
with scrapie offering challenges to scrapie eradication efforts and 2) CWD
spread need not remain geographically confined to current endemic areas, but
could occur anywhere that sheep with scrapie and susceptible cervids cohabitate.
This work demonstrates for the first time that white-tailed deer are susceptible
to sheep scrapie by intracerebral inoculation with a high attack rate and that
the disease that results has similarities to CWD. These experiments will be
repeated with a more natural route of inoculation to determine the likelihood of
the potential transmission of sheep scrapie to white-tailed deer. If scrapie
were to occur in white-tailed deer, results of this study indicate that it would
be detected as a TSE, but may be difficult to differentiate from CWD without
in-depth biochemical analysis.
Wednesday, February 16, 2011
IN CONFIDENCE SCRAPIE TRANSMISSION TO CHIMPANZEES IN CONFIDENCE
THE states are going to have to regulate how many farms that are allowed,
or every state in the USA will wind up being just one big private fenced in game
farm.
kind of like they did with the shrimping industry in the bays, when there
got to be too many shrimp boats, you stop issuing permits, and then lower the
exist number of permits, by not renewing them, due to reduced permits issued.
how many states have $465,000., and can quarantine and purchase there from,
each cwd said infected farm, but how many states can afford this for all the cwd
infected cervid game ranch type farms ???
11,000 game farms X $465,000., do all these game farms have insurance to
pay for this risk of infected the wild cervid herds, in each state ???
Tuesday, December 20, 2011
CHRONIC WASTING DISEASE CWD WISCONSIN Almond Deer (Buckhorn Flats) Farm
Update DECEMBER 2011
The CWD infection rate was nearly 80%, the highest ever in a North American
captive herd.
RECOMMENDATION: That the Board approve the purchase of 80 acres of land for
$465,000 for the Statewide Wildlife Habitat Program in Portage County and
approve the restrictions on public use of the site.
Form 1100-001
(R 2/11)
NATURAL RESOURCES BOARD AGENDA ITEM
SUBJECT: Information Item: Almond Deer Farm Update
FOR: DECEMBER 2011 BOARD MEETING
TUESDAY
TO BE PRESENTED BY TITLE: Tami Ryan, Wildlife Health Section Chief
SUMMARY:
Wednesday, November 14, 2012
PENNSYLVANIA 2012 THE GREAT ESCAPE OF CWD INVESTIGATION MOVES INTO
LOUISIANA and INDIANA
Monday, November 26, 2012
Aerosol Transmission of Chronic Wasting Disease in White-tailed Deer
TSS
posted by Terry S. Singeltary Sr. at
10:28 AM
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