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      Detection of CWD Prions in Urine and Saliva of Deer by Transgenic Mouse Bioassay

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          Abstract

          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[CerPrP] mice). In addition, PrP CWD was detected in pooled and concentrated urine by protein misfolding cyclic amplification (PMCA). The concentration of abnormal prion protein in bodily fluids was very low, as indicated by: undetectable PrP CWD levels by traditional assays (western blot, ELISA) and prolonged incubation periods and incomplete TSE attack rates in inoculated Tg(CerPrP) mice (373 ±3days in 2 of 9 urine-inoculated mice and 342 ±109 days in 8 of 9 saliva-inoculated mice). These findings help extend our understanding of CWD prion shedding and transmission and portend the detection of infectious prions in body fluids in other prion infections.

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          Most cited references31

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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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              Chronic wasting disease.

              Chronic wasting disease (CWD) is a unique transmissible spongiform encephalopathy (TSE) of mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni). The natural history of CWD is incompletely understood, but it differs from scrapie and bovine spongiform encephalopathy (BSE) by virtue of its occurrence in nondomestic and free-ranging species. CWD has many features in common with scrapie, including early widespread distribution of disease-associated prion protein (PrP(d)) in lymphoid tissues, with later involvement of central nervous system (CNS) and peripheral tissues. This distribution likely contributes to apparent efficiency of horizontal transmission and, in this, is similar to scrapie and differs from BSE. Clinical features and lesions of CWD are qualitatively similar to the other animal TSEs. Microscopically, marked spongiform lesions occur in the central nervous system (CNS) after a prolonged incubation period and variable course of clinical disease. During incubation, PrP(d) can be identified in tissues by antibody-based detection systems. Although CWD can be transmitted by intracerebral inoculation to cattle, sheep, and goats, ongoing studies have not demonstrated that domestic livestock are susceptible via oral exposure, the presumed natural route of exposure to TSEs. Surveillance efforts for CWD in captive and free-ranging cervids will continue in concert with similar activities for scrapie and BSE. Eradication of CWD in farmed cervids is the goal of state, federal, and industry programs, but eradication of CWD from free-ranging populations of cervids is unlikely with currently available management techniques.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2009
                18 March 2009
                : 4
                : 3
                : e4848
                Affiliations
                [1 ]Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States of America
                [2 ]Department of Molecular Biology and Genetics, University of Kentucky, Lexington, Kentucky, United States of America
                National Institutes of Health, United States of America
                Author notes

                Conceived and designed the experiments: NJH EAH. Performed the experiments: NJH DMS. Analyzed the data: NJH DMS MDZ GCT EAH. Contributed reagents/materials/analysis tools: NJH MDZ GCT EAH. Wrote the paper: NJH DMS MDZ GCT EAH.

                Article
                08-PONE-RA-07254R2
                10.1371/journal.pone.0004848
                2654070
                19293928
                7676e90a-c76d-4e71-a66e-2eb0f1c7b5e5
                Haley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 8 November 2008
                : 3 February 2009
                Page count
                Pages: 6
                Categories
                Research Article
                Infectious Diseases/Prion Diseases
                Neurological Disorders/Infectious Diseases of the Nervous System
                Pathology/Neuropathology

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                Uncategorized

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