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the structure of the infectious prion protein and its propagation.the prion diseases, which include creutzfeldt-jakob disease in humans, chronic wasting disease in cervids (i.e., deer, elk, moose, and reindeer), bovine spongiform encephalopathy in cattle, as well as sheep and goat scrapie, are caused by the conversion of the cellular prion protein (prp(c)) into a disease-causing conformer (prp(sc)). prp(c) is a regular, gpi-anchored protein that is expressed on the cell surface of neurons and many other cell types. the structure of prp(c) is well studied, base ...201728838667
high prevalence of prion protein genotype associated with resistance to chronic wasting disease in one alberta woodland caribou population.chronic wasting disease (cwd) is a prion disease found in deer, elk and moose in north america and since recently, wild reindeer in norway. caribou are at-risk to encounter cwd in areas such as alberta, canada, where the disease spreads toward caribou habitats. cwd susceptibility is modulated by species-specific polymorphisms in the prion protein gene (prnp). we sequenced prnp of woodland caribou from 9 albertan populations. in one population (chinchaga) a significantly higher frequency of the 1 ...201728350512
molecular mechanisms of chronic wasting disease prion propagation.prion disease epidemics, which have been unpredictable recurrences, are of significant concern for animal and human health. examples include kuru, once the leading cause of death among the fore people in papua new guinea and caused by mortuary feasting; bovine spongiform encephalopathy (bse) and its subsequent transmission to humans in the form of variant creutzfeldt-jakob disease (vcjd), and repeated examples of large-scale prion disease epidemics in animals caused by contaminated vaccines. the ...201728193766
de novo generation of a unique cervid prion strain using protein misfolding cyclic amplification.substantial evidence supports the hypothesis that prions are misfolded, infectious, insoluble, and protease-resistant proteins (prp(res)) devoid of instructional nucleic acid that cause transmissible spongiform encephalopathies (tses). protein misfolding cyclic amplification (pmca) has provided additional evidence that prpres acts as a template that can convert the normal cellular prion protein (prp(c)) present in uninfected normal brain homogenate (nbh) into the infectious misfolded prp(res) is ...201728144628
the structure of mammalian prions and their aggregates.prion diseases, such as creutzfeldt-jakob disease in humans, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids (i.e., deer, elk, moose, and reindeer), and sheep scrapie, are caused by the misfolding of the cellular prion protein (prp(c)) into a disease-causing conformer (prp(sc)). prp(c) is a normal, gpi-anchored protein that is expressed on the surface of neurons and other cell types. the structure of prp(c) is well understood, based on studies of recombinant prp, w ...201728109330
early and non-invasive detection of chronic wasting disease prions in elk feces by real-time quaking induced conversion.chronic wasting disease (cwd) is a fatal prion disease of wild and captive cervids in north america. prions are infectious agents composed of a misfolded version of a host-encoded protein, termed prpsc. infected cervids excrete and secrete prions, contributing to lateral transmission. geographical distribution is expanding and case numbers in wild cervids are increasing. recently, the first european cases of cwd have been reported in a wild reindeer and two moose from norway. therefore, methods ...201627829062
first case of chronic wasting disease in europe in a norwegian free-ranging reindeer.chronic wasting disease (cwd) is a fatal contagious prion disease in cervids that is enzootic in some areas in north america. the disease has been found in deer, elk and moose in the usa and canada, and in south korea following the importation of infected animals. here we report the first case of cwd in europe, in a norwegian free-ranging reindeer in southern norway. the origin of the disease is unknown. until now a low number of cervids, and among them a few reindeer, have been tested for cwd i ...201627641251
chronic wasting disease drives population decline of white-tailed deer.chronic wasting disease (cwd) is an invariably fatal transmissible spongiform encephalopathy of white-tailed deer, mule deer, elk, and moose. despite a 100% fatality rate, areas of high prevalence, and increasingly expanding geographic endemic areas, little is known about the population-level effects of cwd in deer. to investigate these effects, we tested the null hypothesis that high prevalence cwd did not negatively impact white-tailed deer population sustainability. the specific objectives of ...201627575545
caribou consumption in northern canadian communities.chronic wasting disease (cwd) is a transmissible spongiform encephalopathy (tse) found in both farmed and wild deer, elk, and moose in the united states and canada. surveillance efforts in north america identified the geographical distribution of the disease and mechanisms underlying distribution, although the possibility of transmission to other cervids, including caribou, and noncervids, including humans, is not well understood. because of the documented importance of caribou (rangifer tarandu ...201627556568
dietary magnesium and copper affect survival time and neuroinflammation in chronic wasting disease.chronic wasting disease (cwd), the only known wildlife prion disease, affects deer, elk and moose. the disease is an ongoing and expanding problem in both wild and captive north american cervid populations and is difficult to control in part due to the extreme environmental persistence of prions, which can transmit disease years after initial contamination. the role of exogenous factors in cwd transmission and progression is largely unexplored. in an effort to understand the influence of environ ...201627216881
detection of chronic wasting disease in the lymph nodes of free-ranging cervids by real-time quaking-induced conversion.chronic wasting disease (cwd), a transmissible spongiform encephalopathy of deer, elk, and moose, is the only prion disease affecting free-ranging animals. since the disease was first identified in northern colorado and southern wyoming in 1967, new epidemic foci of the disease have been identified in 20 additional states, as well as two canadian provinces and the republic of south korea. identification of cwd-affected animals currently requires postmortem analysis of brain or lymphoid tissues u ...201424958799
mineral licks: motivational factors for visitation and accompanying disease risk at communal use sites of elk and deer.free-ranging cervids acquire most of their essential minerals through forage consumption, though occasionally seek other sources to account for seasonal mineral deficiencies. mineral sources occur as natural geological deposits (i.e., licks) or as anthropogenic mineral supplements. in both scenarios, these sources commonly serve as focal sites for visitation. we monitored 11 licks in rocky mountain national park, north-central colorado, using trail cameras to quantify daily visitation indices (d ...201424711146
potential role of soil properties in the spread of cwd in western canada.chronic wasting disease (cwd) is a horizontally transmissible prion disease of free ranging deer, elk and moose. recent experimental transmission studies indicate caribou are also susceptible to the disease. cwd is present in southeast alberta and southern saskatchewan. this cwd-endemic region is expanding, threatening manitoba and areas of northern alberta and saskatchewan, home to caribou. soil can serve as a stable reservoir for infectious prion proteins; prions bound to soil particles remain ...201624618673
modeling seasonal behavior changes and disease transmission with application to chronic wasting disease.behavior and habitat of wildlife animals change seasonally according to environmental conditions. mathematical models need to represent this seasonality to be able to make realistic predictions about the future of a population and the effectiveness of human interventions. managing and modeling disease in wild animal populations requires particular care in that disease transmission dynamics is a critical consideration in the etiology of both human and animal diseases, with different transmission ...201424035840
introducing a rigid loop structure from deer into mouse prion protein increases its propensity for misfolding in vitro.prion diseases are fatal neurodegenerative disorders characterized by misfolding of the cellular prion protein (prp(c)) into the disease-associated isoform (prp(sc)) that has increased β-sheet content and partial resistance to proteolytic digestion. prion diseases from different mammalian species have varying propensities for transmission upon exposure of an uninfected host to the infectious agent. chronic wasting disease (cwd) is a highly transmissible prion disease that affects free ranging an ...201323825561
early detection of chronic wasting disease prions in urine of pre-symptomatic deer by real-time quaking-induced conversion assay.chronic wasting disease (cwd) is a prion disease of captive and free-ranging deer (odocoileus spp), elk (cervus elaphus nelsonii) and moose (alces alces shirasi). unlike in most other prion diseases, in cwd prions are shed in urine and feces, which most likely contributes to the horizontal transmission within and between cervid species. to date, cwd ante-mortem diagnosis is only possible by immunohistochemical detection of protease resistant prion protein (prp (sc) ) in tonsil or recto-anal muco ...201523764839
experimental chronic wasting disease in wild type vm mice.chronic wasting disease (cwd) is a naturally occurring prion disease in north american deer (odocoileus species), rocky mountain elk (cervus elaphus nelsoni) and moose (alces alces). the disease was first confirmed in the republic of korea in 2001, and subsequent cases were diagnosed in 2004, 2005 and 2010. the experimental host range of cwd includes ferrets, several species of voles, white-footed mice, deer mice and syrian golden hamsters. in addition, cwd was transmitted to the transgenic mous ...201323708962
strain characterization of the korean cwd cases in 2001 and 2004.chronic wasting disease (cwd) has been recognized as a naturally occurring prion disease in north american deer (odocoileus species), rocky mountain elk (cervus elaphus nelsoni) and moose (alces alces). the disease was confirmed only in elk in the republic of korea in 2001, 2004 and 2005. epidemiological investigations showed that cwd was introduced via importation of infected elk from canada between 1994 and 1997. in spite of the increasing geographic distribution and host range of cwd, little ...201322972463
the role of genetics in chronic wasting disease of north american cervids.chronic wasting disease (cwd) is a major concern for the management of north american cervid populations. this fatal prion disease has led to declines in populations which have high cwd prevalence and areas with both high and low infection rates have experienced economic losses in wildlife recreation and fears of potential spill-over into livestock or humans. research from human and veterinary medicine has established that the prion protein gene (prnp) encodes the protein responsible for transmi ...201222460693
occurrence, transmission, and zoonotic potential of chronic wasting disease.chronic wasting disease (cwd) is a fatal, transmissible prion disease that affects captive and free-ranging deer, elk, and moose. although the zoonotic potential of cwd is considered low, identification of multiple cwd strains and the potential for agent evolution upon serial passage hinders a definitive conclusion. surveillance for cwd in free-ranging populations has documented a continual geographic spread of the disease throughout north america. cwd prions are shed from clinically and preclin ...201222377159
evidence for distinct chronic wasting disease (cwd) strains in experimental cwd in ferrets.chronic wasting disease (cwd) is an evolving prion disease of cervids (deer, elk and moose) that has been recognized in north america and korea. infection of non-cervid reservoir or transport species in nature is not reported. however, the ferret (mustela putorius furo) is susceptible to cwd after experimental inoculation. here, we report that infection of ferrets with either of two ferret cwd isolates by various routes of exposure has revealed biologically distinct strain-like properties distin ...201221918005
experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle: comparison to bovine spongiform encephalopathy in cattle.prion diseases or transmissible spongiform encephalopathies (tses) of animals include scrapie of sheep and goats; transmissible mink encephalopathy (tme); chronic wasting disease (cwd) of deer, elk and moose; and bovine spongiform encephalopathy (bse) of cattle. the emergence of bse and its spread to human beings in the form of variant creutzfeldt-jakob disease (vcjd) resulted in interest in susceptibility of cattle to cwd, tme and scrapie. experimental cross-species transmission of tse agents p ...201121908269
chronic wasting disease prion trafficking via the autonomic nervous system.chronic wasting disease (cwd) is a fatal spongiform encephalopathy that is efficiently transmitted among members of the mammalian family cervidae, including deer, elk, and moose. typical of prion diseases, cwd is characterized by the conversion of the native protease-sensitive protein prp(c) to a protease-resistant isoform, denoted prp(res). in native species, spread of the disease likely results from the ingestion of prion-containing excreta, including urine, saliva, or feces. although cervid p ...201121777560
modeling routes of chronic wasting disease transmission: environmental prion persistence promotes deer population decline and extinction.chronic wasting disease (cwd) is a fatal disease of deer, elk, and moose transmitted through direct, animal-to-animal contact, and indirectly, via environmental contamination. considerable attention has been paid to modeling direct transmission, but despite the fact that cwd prions can remain infectious in the environment for years, relatively little information exists about the potential effects of indirect transmission on cwd dynamics. in the present study, we use simulation models to demonstr ...201121603638
chronic wasting disease.chronic wasting disease (cwd) is a prion disease of free-ranging and farmed ungulates (deer, elk, and moose) in north america and south korea. first described by the late e.s. williams and colleagues in northern colorado and southern wyoming in the 1970s, cwd has increased tremendously both in numerical and geographical distribution, reaching prevalence rates as high as 50% in free-ranging and >90% in captive deer herds in certain areas of usa and canada. cwd is certainly the most contagious pri ...201121598099
fate of prions in soil: a review.prions are the etiological agents of transmissible spongiform encephalopathies (tsses), a class of fatal neurodegenerative diseases affecting humans and other mammals. the pathogenic prion protein is a misfolded form of the host-encoded prion protein and represents the predominant, if not sole, component of the infectious agent. environmental routes of tse transmission areimplicated in epizootics of sheep scrapie and chronic wasting disease (cwd) of deer, elk, and moose. soil represents a plausi ...201121520752
association analysis of prnp gene region with chronic wasting disease in rocky mountain elk.abstract:201021087518
chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein.chronic wasting disease (cwd) is a prion disease that affects free-ranging and captive cervids, including mule deer, white-tailed deer, rocky mountain elk and moose. cwd-infected cervids have been reported in 14 usa states, two canadian provinces and in south korea. the possibility of a zoonotic transmission of cwd prions via diet is of particular concern in north america where hunting of cervids is a popular sport. to investigate the potential public health risks posed by cwd prions, we have in ...201020610667
pathogenesis of chronic wasting disease in cervidized transgenic mice.chronic wasting disease (cwd) is a fatal, endemic prion disease of wild and captive cervids, including deer, elk, and moose. typical of prion diseases, cwd is characterized by the conversion of the native, protease-sensitive protein prp(c) to a protease-resistant isoform, denoted as prp(res). here we have studied the expression of cervid prp(c) and the pathogenesis of cwd infection in transgenic mice expressing the normal cervid prion protein (tg[cerprp] mice). using tissue-based in situ immunoh ...201020395435
susceptibilities of nonhuman primates to chronic wasting disease.chronic wasting disease (cwd) is a transmissible spongiform encephalopathy, or prion disease, that affects deer, elk, and moose. human susceptibility to cwd remains unproven despite likely exposure to cwd-infected cervids. we used 2 nonhuman primate species, cynomolgus macaques and squirrel monkeys, as human models for cwd susceptibility. cwd was inoculated into these 2 species by intracerebral and oral routes. after intracerebral inoculation of squirrel monkeys, 7 of 8 cwd isolates induced a cl ...200919788803
detection of cwd prions in urine and saliva of deer by transgenic mouse bioassay.chronic wasting disease (cwd) is a prion disease affecting captive and free-ranging cervids (e.g. deer, elk, and moose). the mechanisms of cwd transmission are poorly understood, though bodily fluids are thought to play an important role. here we report the presence of infectious prions in the urine and saliva of deer with chronic wasting disease (cwd). prion infectivity was detected by bioassay of concentrated, dialyzed urine and saliva in transgenic mice expressing the cervid prp gene (tg[cerp ...200919293928
persistent bovine viral diarrhea virus infection in wild cervids of colorado.bovine viral diarrhea virus (bvdv) is a significant viral pathogen of domestic cattle. worldwide, there is evidence of bvdv exposure and infection in wild ungulates; however, the frequency and significance of such events are unknown. to determine the prevalence and distribution of colorado deer, elk, and moose persistently infected (pi) with bvdv, a cross-sectional study was conducted using full-thickness ear tissue samples collected from animals presented to the colorado division of wildlife fo ...200818776103
experimental chronic wasting disease (cwd) in the ferret.chronic wasting disease (cwd), a prion disease of north american deer, elk and moose, affects both free-ranging and captive cervids. the potential host range for cwd remains uncertain. the susceptibility of the ferret to cwd was examined experimentally by administering infectious brain material by the intracerebral (ic) or oral (po) route. between 15 and 20 months after ic inoculation, ferrets developed neurological signs consistent with prion disease, including polyphagia, somnolence, piloerect ...200818387626
a prion disease of cervids: chronic wasting disease.chronic wasting disease (cwd) is a prion disease of deer, elk, and moose, initially recognized in colorado mule deer. the discovery of cwd beyond the borders of colorado and wyoming, in canada and as far east as new york, has led to its emergence as a prion disease of international importance. epidemiological studies indicate that cwd is horizontally transmitted among free-ranging animals, potentially indirectly by prion-containing secreta or excreta contaminating the environment. experimental c ...200818381058
molecular characterization of the rocky mountain elk (cervus elaphus nelsoni) prnp putative promoter.chronic wasting disease (cwd) is a transmissible spongiform encephalopathy (tse) affecting deer (odocoileus spp.), moose (alces alces), and rocky mountain elk (cervus elaphus nelsoni). leucine homozygosity at elk prnp codon 132 has been associated with reduced cwd susceptibility. however, naturally acquired cwd has been detected in elk possessing the 132 leu/leu genotype. recent human and bovine studies indicate that prnp regulatory polymorphisms may also influence tse occurrence. therefore, we ...200718032463
species barriers for chronic wasting disease by in vitro conversion of prion protein.chronic wasting disease (cwd) is a transmissible spongiform encephalopathy that can affect north american cervids (deer, elk, and moose). using a novel in vitro conversion system based on incubation of prions with normal brain homogenates, we now report that prp(cwd) of elk can readily induce the conversion of normal cervid prp (prp(c)) molecules to a protease-resistant form, but is less efficient in converting the prp(c) of other species, such as human, bovine, hamster, and mouse. however, when ...200717964288
a natural case of chronic wasting disease in a free-ranging moose (alces alces shirasi).chronic wasting disease (cwd) was diagnosed in a free-ranging moose (alces alces shirasi) killed by a hunter in jackson county, colorado, usa, in september 2005. the diagnosis was based upon immunohistochemistry (ihc) demonstrating the presence of accumulations of cwd-associated prion protein (prp(cwd)) in tissue sections of medulla oblongata at the level of the obex (dorsal motor nucleus of the vagus) and in retropharyngeal lymph node (rpln); additional testing by ihc revealed deposits of prp(c ...200717495319
oral transmission of chronic wasting disease in captive shira's moose.three captive shira's moose (alces alces shirasi) were orally inoculated with a single dose (5 g) of whole-brain homogenate prepared from chronic wasting disease (cwd)-affected mule deer (odocoileus hemionus). all moose died of causes thought to be other than cwd. histologic examination of one female moose dying 465 days postinoculation revealed spongiform change in the neuropil, typical of transmissible spongiform encephalopathy. immunohistochemistry staining for the proteinase-resistant isofor ...200617092895
prion protein in cardiac muscle of elk (cervus elaphus nelsoni) and white-tailed deer (odocoileus virginianus) infected with chronic wasting disease.to investigate the possible presence of disease-associated prion protein (prp(d)) in striated muscle of chronic wasting disease (cwd)-affected cervids, samples of diaphragm, tongue, heart and three appendicular skeletal muscles from mule deer (odocoileus hemionus), white-tailed deer (odocoileus virginianus), elk (cervus elaphus nelsoni) and moose (alces alces shirasi) were examined by elisa, western immunoblot and immunohistochemistry (ihc). prp(d) was detected in samples of heart muscle from se ...200617030881
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