Direct prion neuroinvasion following inhalation into the nasal cavity.

Inhalation of prions into the nasal cavity is an efficient route of infection. Following inhalation of infectious prions, animals develop disease with a similar incubation period compared with per os exposure, but with greater efficiency. To identify the reason for this increased efficiency, we identified neural structures that uniquely innervate the nasal cavity and neural structures known to mediate neuroinvasion following oral infection and used immunohistochemistry to determine the temporal and spatial accumulation of prions from hamster tissue sections containing cell bodies and axons at 2-week intervals following prion exposure.

Expression of the cellular prion protein by mast cells in white-tailed deer carotid body, cervical lymph nodes and ganglia.

Chronic wasting disease (CWD) is a transmissible and fatal prion disease that affects cervids. While both oral and nasal routes of exposure to prions cause disease, the spatial and temporal details of how prions enter the central nervous system (CNS) are unknown. Carotid bodies (CBs) are structures that are exposed to blood-borne prions and are densely innervated by nerves that are directly connected to brainstem nuclei, known to be early sites of prion neuroinvasion.

Rapid and sensitive determination of residual prion infectivity from prion-decontaminated surfaces.

Prion diseases are untreatable fatal transmissible neurodegenerative diseases that affect a wide range of mammals, including humans, and are caused by PrP, the infectious self-templating conformation of the host-encoded protein, PrP. Prion diseases can be transmitted via surfaces (e.g.

Effect of host and strain factors on α-synuclein prion pathogenesis.

Prion diseases are a group of neurodegenerative disorders caused by misfolding of proteins into pathogenic conformations that self-template to spread disease. Although this mechanism is largely associated with the prion protein (PrP) in classical prion diseases, a growing literature indicates that other proteins, including α-synuclein, rely on a similar disease mechanism. Notably, α-synuclein misfolds into distinct conformations, or strains, that cause discrete clinical disorders including multiple system atrophy (MSA) and Parkinson's disease (PD).

Prion forensics: a multidisciplinary approach to investigate CWD at an illegal deer carcass disposal site.

Infectious prions are resistant to degradation and remain infectious in the environment for several years. Chronic wasting disease (CWD) has been detected in cervids inhabiting North America, the Nordic countries, and South Korea. CWD-prion spread is partially attributed to carcass transport and disposal.

Chronic Wasting Disease: State of the Science.

Chronic wasting disease (CWD) is a prion disease affecting cervid species, both free-ranging and captive populations. As the geographic range continues to expand and disease prevalence continues to increase, CWD will have an impact on cervid populations, local economies, and ecosystem health. Mitigation of this "wicked" disease will require input from many different stakeholders including hunters, landowners, research biologists, wildlife managers, and others, working together.

Strain-Specific Targeting and Destruction of Cells by Prions.

Prion diseases are caused by the disease-specific self-templating infectious conformation of the host-encoded prion protein, PrP. Prion strains are operationally defined as a heritable phenotype of disease under controlled conditions. One of the hallmark phenotypes of prion strain diversity is tropism within and between tissues.

Evidence for preexisting prion substrain diversity in a biologically cloned prion strain.

Prion diseases are a group of inevitably fatal neurodegenerative disorders affecting numerous mammalian species, including Sapiens. Prions are composed of PrPSc, the disease specific conformation of the host encoded prion protein. Prion strains are operationally defined as a heritable phenotype of disease under controlled transmission conditions.

Expression of the cellular prion protein by mast cells in the human carotid body.

Prion diseases are fatal neurologic disorders that can be transmitted by blood transfusion. The route for neuroinvasion following exposure to infected blood is not known. Carotid bodies (CBs) are specialized chemosensitive structures that detect the concentration of blood gasses and provide feedback for the neural control of respiration.

Prion protein amino acid sequence influences formation of authentic synthetic PrP.

Synthetic prions, generated de novo from minimal, non-infectious components, cause bona fide prion disease in animals. Transmission of synthetic prions to hosts expressing syngeneic PrP results in extended, variable incubation periods and incomplete attack rates. In contrast, murine synthetic prions (MSP) generated via PMCA with minimal cofactors readily infected mice and hamsters and rapidly adapted to both species.

Prion strains: shining new light on old concepts.

Prion diseases are a group of inevitably fatal neurodegenerative disorders affecting numerous mammalian species, including humans. The existence of heritable phenotypes of disease in the natural host suggested that prions exist as distinct strains. Transmission of sheep scrapie to rodent models accelerated prion research, resulting in the isolation and characterization of numerous strains with distinct characteristics.

Sensitive detection of chronic wasting disease prions recovered from environmentally relevant surfaces.

Chronic wasting disease (CWD) has been identified in 30 states in the United States, four provinces in Canada, and recently emerged in Scandinavia. The association of CWD prions with environmental materials such as soil, plants, and surfaces may enhance the persistence of CWD prion infectivity in the environment exacerbating disease transmission. Identifying and quantifying CWD prions in the environment is significant for prion monitoring and disease transmission control.

Assessment of Real-Time Quaking-Induced Conversion (RT-QuIC) Assay, Immunohistochemistry and ELISA for Detection of Chronic Wasting Disease under Field Conditions in White-Tailed Deer: A Bayesian Approach.

Chronic wasting disease (CWD) is a transmissible prion disease of the family. ELISA and IHC tests performed postmortem on the medial retropharyngeal lymph nodes (RPLN) or obex are considered diagnostic gold standards for prion detection. However, differences in CWD transmission, stage of infection, pathogenesis, and strain can limit performance.

Transport of Prions in the Peripheral Nervous System: Pathways, Cell Types, and Mechanisms.

Prion diseases are transmissible protein misfolding disorders that occur in animals and humans where the endogenous prion protein, PrP, undergoes a conformational change into self-templating aggregates termed PrP. Formation of PrP in the central nervous system (CNS) leads to gliosis, spongiosis, and cellular dysfunction that ultimately results in the death of the host. The spread of prions from peripheral inoculation sites to CNS structures occurs through neuroanatomical networks.

Efficient interspecies transmission of synthetic prions.

Prions are comprised solely of PrPSc, the misfolded self-propagating conformation of the cellular protein, PrPC. Synthetic prions are generated in vitro from minimal components and cause bona fide prion disease in animals. It is unknown, however, if synthetic prions can cross the species barrier following interspecies transmission.

Environmental and host factors that contribute to prion strain evolution.

Prions are novel pathogens that are composed entirely of PrP, the self-templating conformation of the host prion protein, PrP. Prion strains are operationally defined as a heritable phenotype of disease that are encoded by strain-specific conformations of PrP. The factors that influence the relative distribution of strains in a population are only beginning to be understood.

The role of prion strain diversity in the development of successful therapeutic treatments.

Prions are a self-propagating misfolded conformation of a cellular protein. Prions are found in several eukaryotic organisms with mammalian prion diseases encompassing a wide range of disorders. The first recognized prion disease, the transmissible spongiform encephalopathies (TSEs), affect several species including humans.

Failure To Detect Prion Infectivity in Ticks following Prion-Infected Blood Meal.

Chronic wasting disease (CWD) is an emerging and fatal contagious prion disease that affects cervids, including mule deer, white-tailed deer, black-tailed deer, red deer reindeer, elk, and moose. CWD prions are widely distributed throughout the bodies of CWD-infected animals and are found in the nervous system, lymphoid tissues, muscle, blood, urine, feces, and antler velvet. The mechanism of CWD transmission in natural settings is unknown.

Incomplete glycosylation during prion infection unmasks a prion protein epitope that facilitates prion detection and strain discrimination.

The causative factors underlying conformational conversion of cellular prion protein (PrP) into its infectious counterpart (PrP) during prion infection remain undetermined, in part because of a lack of monoclonal antibodies (mAbs) that can distinguish these conformational isoforms. Here we show that the anti-PrP mAb PRC7 recognizes an epitope that is shielded from detection when glycans are attached to Asn-196. We observed that whereas PrP is predisposed to full glycosylation and is therefore refractory to PRC7 detection, prion infection leads to diminished PrP glycosylation at Asn-196, resulting in an unshielded PRC7 epitope that is amenable to mAb recognition upon renaturation.

Underglycosylated prion protein modulates plaque formation in the brain.

The prion agent is unique in biology and is comprised of prion protein scrapie (PrPSc), a self-templating conformational variant of the host encoded prion protein cellular (PrPC). The deposition patterns of PrPSc in the CNS can vary considerably from a diffuse synaptic pattern to large plaque-like aggregates. Alterations of PrPC posttranslational processing can change PrPSc deposition patterns; however, the mechanism underlying these observations is unclear.

Cellular prion protein gene polymorphisms linked to differential scrapie susceptibility correlate with distinct residue connectivity between secondary structure elements.

The conformational conversion of the cellular prion protein (PrP) to the misfolded and aggregated isoform, termed scrapie prion protein (PrP), is key to the development of a group of neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs). Although the conversion mechanism is not fully understood, the role of gene polymorphisms in varying susceptibilities to prion diseases is well established. In ovine, specific gene polymorphisms in PrP alter prion disease susceptibility: the Valine136-Glutamine171 variant ( structure) displays high susceptibility to classical scrapie while the Alanine136-Arginine171 variant ( structure) displays reduced susceptibility.

Alteration of Prion Strain Emergence by Nonhost Factors.

Prions can persist in the environment for extended periods of time after adsorption to surfaces, including soils, feeding troughs, or fences. Prion strain- and soil-specific differences in prion adsorption, infectivity, and response to inactivation may be involved in strain maintenance or emergence of new strains in a population. Extensive proteinase K (PK) digestion of Hyper (HY) and Drowsy (DY) PrP resulted in a greater reduction in the level of DY PrP than of HY PrP Use of the PK-digested material in protein misfolding cyclic amplification strain interference (PMCAsi) resulted in earlier emergence of HY PrP than of undigested controls.