Document Detail


Accelerated shedding of prions following damage to the olfactory epithelium.
MedLine Citation:
PMID:  22130543     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study, we investigated the role of damage to the nasal mucosa in the shedding of prions into nasal samples as a pathway for prion transmission. Here, we demonstrate that prions can replicate to high levels in the olfactory sensory epithelium (OSE) in hamsters and that induction of apoptosis in olfactory receptor neurons (ORNs) in the OSE resulted in sloughing off of the OSE from nasal turbinates into the lumen of the nasal airway. In the absence of nasotoxic treatment, olfactory marker protein (OMP), which is specific for ORNs, was not detected in nasal lavage samples. However, after nasotoxic treatment that leads to apoptosis of ORNs, both OMP and prion proteins were present in nasal lavage samples. The cellular debris that was released from the OSE into the lumen of the nasal airway was positive for both OMP and the disease-specific isoform of the prion protein, PrP(Sc). By using the real-time quaking-induced conversion assay to quantify prions, a 100- to 1,000-fold increase in prion seeding activity was observed in nasal lavage samples following nasotoxic treatment. Since neurons replicate prions to higher levels than other cell types and ORNs are the most environmentally exposed neurons, we propose that an increase in ORN apoptosis or damage to the nasal mucosa in a host with a preexisting prion infection of the OSE could lead to a substantial increase in the release of prion infectivity into nasal samples. This mechanism of prion shedding from the olfactory mucosa could contribute to prion transmission.
Authors:
Richard A Bessen; Jason M Wilham; Diana Lowe; Christopher P Watschke; Harold Shearin; Scott Martinka; Byron Caughey; James A Wiley
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-11-30
Journal Detail:
Title:  Journal of virology     Volume:  86     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-16     Completed Date:  2012-04-09     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1777-88     Citation Subset:  IM    
Affiliation:
Department of Immunology and Infectious Diseases, Montana State University, Bozeman, Montana, USA. rbessen@montana.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Humans
Olfactory Mucosa / pathology*
Prions / metabolism*
Grant Support
ID/Acronym/Agency:
P20 RR020185/RR/NCRR NIH HHS; R01 AI055043/AI/NIAID NIH HHS; R01 AI055043/AI/NIAID NIH HHS; R21 AI084094/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Prions
Comments/Corrections

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