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      Experimental Oral Transmission of Chronic Wasting Disease to Reindeer ( Rangifer tarandus tarandus)

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          Abstract

          Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, remains prevalent in North American elk, white-tailed deer and mule deer. A natural case of CWD in reindeer ( Rangifer tarandus tarandus) has not been reported despite potential habitat overlap with CWD-infected deer or elk herds. This study investigates the experimental transmission of CWD from elk or white-tailed deer to reindeer by the oral route of inoculation. Ante-mortem testing of the three reindeer exposed to CWD from white-tailed deer identified the accumulation of pathological PrP (PrP CWD) in the recto-anal mucosa associated lymphoid tissue (RAMALT) of two reindeer at 13.4 months post-inoculation. Terminal CWD occurred in the two RAMALT-positive reindeer at 18.5 and 20 months post-inoculation while one other reindeer in the white-tailed deer CWD inoculum group and none of the 3 reindeer exposed to elk CWD developed disease. Tissue distribution analysis of PrP CWD in CWD-affected reindeer revealed widespread deposition in central and peripheral nervous systems, lymphoreticular tissues, the gastrointestinal tract, neuroendocrine tissues and cardiac muscle. Analysis of prion protein gene ( PRNP) sequences in the 6 reindeer identified polymorphisms at residues 2 (V/M), 129 (G/S), 138 (S/N) and 169 (V/M). These findings demonstrate that (i) a sub-population of reindeer are susceptible to CWD by oral inoculation implicating the potential for transmission to other Rangifer species, and (ii) certain reindeer PRNP polymorphisms may be protective against CWD infection.

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          Environmental Sources of Prion Transmission in Mule Deer

          Whether transmission of the chronic wasting disease (CWD) prion among cervids requires direct interaction with infected animals has been unclear. We report that CWD can be transmitted to susceptible animals indirectly, from environments contaminated by excreta or decomposed carcasses. Under experimental conditions, mule deer (Odocoileus hemionus) became infected in two of three paddocks containing naturally infected deer, in two of three paddocks where infected deer carcasses had decomposed in situ ≈1.8 years earlier, and in one of three paddocks where infected deer had last resided 2.2 years earlier. Indirect transmission and environmental persistence of infectious prions will complicate efforts to control CWD and perhaps other animal prion diseases.
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            Chronic wasting disease of captive mule deer: a spongiform encephalopathy.

            In the past 12 years (1967-79) a syndrome we identify as chronic wasting disease has been observed in 53 mule deer (Odocoileus hemionus hemionus) and one black-tailed deer (Odocoileus hemionus columbianus) held in captivity in several wildlife facilities in Colorado and more recently in Wyoming. Clinical signs were seen in adult deer and included behavioral alterations, progressive weight loss and death in 2 weeks to 8 months. Gross necropsy findings included emaciation and excess rumen fluid admixed with sand and gravel. Consistent histopathologic change was limited to the central nervous system and characterized by widespread spongiform transformation of the neuropil, single of multiple intracytoplasmic vacuoles in neuronal perikaryons and intense astrocytic hypertrophy and hyperplasia. Presented is a clinical characterization of chronic wasting disease and pathologic evidence supporting the conclusion that the disease is a specific spontaneously occurring form of spongiform encephalopathy.
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              Prion strain mutation determined by prion protein conformational compatibility and primary structure.

              Prions are infectious proteins composed of the abnormal disease-causing isoform PrPSc, which induces conformational conversion of the host-encoded normal cellular prion protein PrPC to additional PrPSc. The mechanism underlying prion strain mutation in the absence of nucleic acids remains unresolved. Additionally, the frequency of strains causing chronic wasting disease (CWD), a burgeoning prion epidemic of cervids, is unknown. Using susceptible transgenic mice, we identified two prevalent CWD strains with divergent biological properties but composed of PrPSc with indistinguishable biochemical characteristics. Although CWD transmissions indicated stable, independent strain propagation by elk PrPC, strain coexistence in the brains of deer and transgenic mice demonstrated unstable strain propagation by deer PrPC. The primary structures of deer and elk prion proteins differ at residue 226, which, in concert with PrPSc conformational compatibility, determines prion strain mutation in these cervids.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                18 June 2012
                : 7
                : 6
                : e39055
                Affiliations
                [1 ]National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa Laboratory – Fallowfield, Ottawa, Ontario, Canada
                [2 ]Departments of Pathology and Medicine, University of California, San Diego, La Jolla, California, United States of America
                [3 ]Department of Pathology, Microbiology and Immunology, University of California, Davis, California, United States of America
                [4 ]Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Pullman, Washington, United States of America
                [5 ]Veterinary Diagnostic Laboratory, Colorado State University, Fort Collins, Colorado, United States of America
                Creighton University, United States of America
                Author notes

                Conceived and designed the experiments: AB GBM. Performed the experiments: GBM CJS KIO JA NPH IW TRS. Analyzed the data: GBM CJS KIO NPH IW TRS AB. Contributed reagents/materials/analysis tools: CJS KIO TRS AB. Wrote the paper: GBM CJS AB.

                Article
                PONE-D-12-12754
                10.1371/journal.pone.0039055
                3377593
                22723928
                ff219b79-56d6-47c5-a3c4-d5f0a222251e
                This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
                History
                : 4 May 2012
                : 15 May 2012
                Page count
                Pages: 8
                Categories
                Research Article
                Biology
                Neuroscience
                Neurobiology of Disease and Regeneration
                Veterinary Science
                Animal Types
                Large Animals
                Wildlife
                Veterinary Anatomy and Physiology
                Veterinary Diseases
                Zoonotic Diseases
                Prion Diseases
                Veterinary Prion Diseases
                Veterinary Medicine
                Veterinary Diagnostics
                Veterinary Pathology

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                Uncategorized

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