Abstract:
:This study investigated the role of prion infection of the olfactory mucosa in the shedding of prion infectivity into nasal secretions. Prion infection with the HY strain of the transmissible mink encephalopathy (TME) agent resulted in a prominent infection of the olfactory bulb and the olfactory sensory epithelium including the olfactory receptor neurons (ORNs) and vomeronasal receptor neurons (VRNs), whose axons comprise the two olfactory cranial nerves. A distinct glycoform of the disease-specific isoform of the prion protein, PrP(Sc), was found in the olfactory mucosa compared to the olfactory bulb, but the total amount of HY TME infectivity in the nasal turbinates was within 100-fold of the titer in the olfactory bulb. PrP(Sc) co-localized with olfactory marker protein in the soma and dendrites of ORNs and VRNs and also with adenylyl cyclase III, which is present in the sensory cilia of ORNs that project into the lumen of the nasal airway. Nasal lavages from HY TME-infected hamsters contained prion titers as high as 10(3.9) median lethal doses per ml, which would be up to 500-fold more infectious in undiluted nasal fluids. These findings were confirmed using the rapid PrP(Sc) amplification QuIC assay, indicating that nasal swabs have the potential to be used for prion diagnostics. These studies demonstrate that prion infection in the olfactory epithelium is likely due to retrograde spread from the olfactory bulb along the olfactory and vomeronasal axons to the soma, dendrites, and cilia of these peripheral neurons. Since prions can replicate to high levels in neurons, we propose that ORNs can release prion infectivity into nasal fluids. The continual turnover and replacement of mature ORNs throughout the adult lifespan may also contribute to prion shedding from the nasal passage and could play a role in transmission of natural prion diseases in domestic and free-ranging ruminants.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Bessen RA,Shearin H,Martinka S,Boharski R,Lowe D,Wilham JM,Caughey B,Wiley JAdoi
10.1371/journal.ppat.1000837subject
Has Abstractpub_date
2010-04-15 00:00:00pages
e1000837issue
4eissn
1553-7366issn
1553-7374journal_volume
6pub_type
杂志文章相关文献
PLoS Pathogens文献大全abstract::The picornaviruses coxsackievirus A24 variant (CVA24v) and enterovirus 70 (EV70) cause continued outbreaks and pandemics of acute hemorrhagic conjunctivitis (AHC), a highly contagious eye disease against which neither vaccines nor antiviral drugs are currently available. Moreover, these viruses can cause symptoms in t...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004401
更新日期:2014-10-16 00:00:00
abstract::Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infection more broadly. Viral receptor utilization is a major determinant of cell tropism, host range, and pathogenesis. The bona fide receptor for HNoV is unknown. Recently, we identified CD300lf as a proteinaceous receptor for ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008242
更新日期:2020-04-06 00:00:00
abstract::The agr quorum-sensing system of Staphylococcus aureus modulates the expression of virulence factors in response to autoinducing peptides (AIPs). Recent studies have suggested a role for the agr system in S. aureus biofilm development, as agr mutants exhibit a high propensity to form biofilms, and cells dispersing fro...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000052
更新日期:2008-04-25 00:00:00
abstract::My father was diagnosed with stomach cancer recently. Luckily, it was still at an early stage, and endoscopic surgery successfully took care of it. My father was fortunate; since people with stomach cancer do not show clear symptoms in the early stages, the disease is often not diagnosed until it becomes advanced. In ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006420
更新日期:2017-08-10 00:00:00
abstract::Transforming growth factor (TGF)-β inhibits hepatitis B virus (HBV) replication although the intracellular effectors involved are not determined. Here, we report that reduction of HBV transcripts by TGF-β is dependent on AID expression, which significantly decreases both HBV transcripts and viral DNA, resulting in inh...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004780
更新日期:2015-04-02 00:00:00
abstract::Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that persists lifelong in the host. In ∼4% of infected people, HTLV-1 causes a chronic disabling neuroinflammatory disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The pathogenesis of HAM/TSP is unknown and treatment remain...
journal_title:PLoS pathogens
pub_type: 临床试验,杂志文章
doi:10.1371/journal.ppat.1002480
更新日期:2012-01-01 00:00:00
abstract::Unlike the pandemic form of HIV-1 (group M), group O viruses are endemic in west central Africa, especially in Cameroon. However, little is known about group O's genetic evolution, and why this highly divergent lineage has not become pandemic. Using a unique and large set of group O sequences from samples collected fr...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005029
更新日期:2015-08-04 00:00:00
abstract::Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibiotic resistance and impairment of innate immunity by disease processes and steroid therapy. Manipulation miRNA directly regulating anti-micro...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004549
更新日期:2015-04-20 00:00:00
abstract::Cells of the innate immune system act in synergy to provide a first line of defense against pathogens. Here we describe that dendritic cells (DCs), matured with viral products or mimics thereof, including Epstein-Barr virus (EBV), activated natural killer (NK) cells more efficiently than other mature DC preparations. ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.0040027
更新日期:2008-02-08 00:00:00
abstract::Cerebrovascular dysfunction plays a key role in the pathogenesis of cerebral malaria. In experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA, cerebrovascular dysfunction characterized by vascular constriction, occlusion and damage results in impaired perfusion and reduced cerebral blood flow and oxy...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1003444
更新日期:2013-01-01 00:00:00
abstract::Human cytomegalovirus (HCMV) is a widely distributed herpesvirus that causes significant morbidity in immunocompromised hosts. Inhibitors of viral DNA replication are available, but adverse effects limit their use. Alternative antiviral strategies may include inhibition of entry. We show that soluble derivatives of th...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006273
更新日期:2017-04-12 00:00:00
abstract::The interplay between autophagy and intracellular pathogens is intricate as autophagy is an essential cellular response to fight against infections, whereas numerous microbes have developed strategies to escape this process or even exploit it to their own benefit. The fine tuned timing and/or selective molecular pathw...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1003599
更新日期:2013-01-01 00:00:00
abstract::To better understand the initiation of CD8(+) T cell responses during infection, the primary response to the intracellular parasite Toxoplasma gondii was characterized using 2-photon microscopy combined with an experimental system that allowed visualization of dendritic cells (DCs) and parasite specific CD8(+) T cells...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000505
更新日期:2009-07-01 00:00:00
abstract::Since the advent of genome-wide small interfering RNA screening, large numbers of cellular cofactors important for viral infection have been discovered at a rapid pace, but the viral targets and the mechanism of action for many of these cofactors remain undefined. One such cofactor is cyclophilin A (CyPA), upon which ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1001118
更新日期:2010-09-23 00:00:00
abstract::In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenit...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005755
更新日期:2016-07-07 00:00:00
abstract::Dissemination of HIV in the host involves transit of the virus and virus-infected cells across the lymphatic endothelium. HIV may alter lymphatic endothelial permeability to foster dissemination, but the mechanism is largely unexplored. Using a primary human lymphatic endothelial cell model, we found that HIV-1 envelo...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1002461
更新日期:2012-01-01 00:00:00
abstract::Paramyxoviruses are known to replicate in the cytoplasm and bud from the plasma membrane. Matrix is the major structural protein in paramyxoviruses that mediates viral assembly and budding. Curiously, the matrix proteins of a few paramyxoviruses have been found in the nucleus, although the biological function associat...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1001186
更新日期:2010-11-11 00:00:00
abstract::Legionella pneumophila translocates multiple bacterial effector proteins into host cells to direct formation of a replication vacuole for the bacterium. The emerging consensus is that formation of this compartment involves recruitment of membrane material that traffics between the endoplasmic reticulum (ER) and Golgi....
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.0020034
更新日期:2006-04-01 00:00:00
abstract::Human T Lymphotropic virus (HTLV) infection can persist in individuals resulting, at least in part, from viral escape of the innate immunity, including inhibition of type I interferon response in infected T-cells. Plasmacytoid dendritic cells (pDCs) are known to bypass viral escape by their robust type I interferon pr...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1007589
更新日期:2019-02-28 00:00:00
abstract::Staphylococcus aureus is a major human pathogen causing a wide spectrum of nosocomial and community-associated infections with high morbidity and mortality. S. aureus generates a large number of virulence factors whose timing and expression levels are precisely tuned by regulatory proteins and RNAs. The aptitude of ba...
journal_title:PLoS pathogens
pub_type: 杂志文章,评审
doi:10.1371/journal.ppat.1002006
更新日期:2011-03-01 00:00:00
abstract::Type III secretion systems (T3SS) are nano-syringes used by a wide range of Gram-negative pathogens to promote infection by directly injecting effector proteins into targeted host cells. Translocation of effectors is triggered by host-cell contact and requires assembly of a pore in the host-cell plasma membrane, which...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005530
更新日期:2016-03-29 00:00:00
abstract::The process by which drug-resistant HIV-1 arises and spreads spatially within an infected individual is poorly understood. Studies have found variable results relating how HIV-1 in the blood differs from virus sampled in tissues, offering conflicting findings about whether HIV-1 throughout the body is homogeneously di...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006358
更新日期:2017-05-25 00:00:00
abstract::Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To eluc...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006096
更新日期:2017-01-04 00:00:00
abstract::Many biological processes are controlled by intricate networks of transcriptional regulators. With the development of microarray technology, transcriptional changes can be examined at the whole-genome level. However, such analysis often lacks information on the hierarchical relationship between components of a given s...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.0020123
更新日期:2006-11-01 00:00:00
abstract::Fusogenic reoviruses encode fusion-associated small transmembrane (FAST) protein, which induces cell-cell fusion. FAST protein is the only known fusogenic protein in non-enveloped viruses, and its role in virus replication is not yet known. We generated replication-competent, FAST protein-deficient pteropine orthoreov...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1007675
更新日期:2019-04-25 00:00:00
abstract::Kaposi's sarcoma-associated herpesvirus (KSHV) vGPCR is a constitutively active G protein-coupled receptor that subverts proliferative and inflammatory signaling pathways to induce cell transformation in Kaposi's sarcoma. Cyclooxygenase-2 (COX-2) is an inflammatory mediator that plays a key regulatory role in the acti...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1009006
更新日期:2020-10-15 00:00:00
abstract::Specific types of human papillomaviruses (HPVs) cause cervical cancer. Cervical cancers exhibit aberrant cellular microRNA (miRNA) expression patterns. By genome-wide analyses, we investigate whether the intracellular and exosomal miRNA compositions of HPV-positive cancer cells are dependent on endogenous E6/E7 oncoge...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004712
更新日期:2015-03-11 00:00:00
abstract::In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral on...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004980
更新日期:2015-06-18 00:00:00
abstract::Vibrio cholerae has evolved to adeptly transition between the human small intestine and aquatic environments, leading to water-borne spread and transmission of the lethal diarrheal disease cholera. Using a host model that mimics the pathology of human cholera, we applied high density transposon mutagenesis combined wi...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1003800
更新日期:2013-01-01 00:00:00
abstract::Positive-strand RNA viruses replicate in host cells by forming large viral replication organelles, which harbor numerous membrane-bound viral replicase complexes (VRCs). In spite of its essential role in viral replication, the biogenesis of the VRCs is not fully understood. The authors identified critical roles of cel...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1009120
更新日期:2020-12-28 00:00:00