Abstract
Infectious prion diseases1—scrapie of sheep2 and chronic wasting disease (CWD) of several species in the deer family3,4—are transmitted naturally within affected host populations. Although several possible sources of contagion have been identified in excretions and secretions from symptomatic animals5,6,7,8, the biological importance of these sources in sustaining epidemics remains unclear. Here we show that asymptomatic CWD-infected mule deer (Odocoileus hemionus) excrete CWD prions in their faeces long before they develop clinical signs of prion disease. Intracerebral inoculation of irradiated deer faeces into transgenic mice overexpressing cervid prion protein (PrP) revealed infectivity in 14 of 15 faecal samples collected from five deer at 7–11 months before the onset of neurological disease. Although prion concentrations in deer faeces were considerably lower than in brain tissue from the same deer collected at the end of the disease, the estimated total infectious dose excreted in faeces by an infected deer over the disease course may approximate the total contained in a brain. Prolonged faecal prion excretion by infected deer provides a plausible natural mechanism that might explain the high incidence and efficient horizontal transmission of CWD within deer herds3,4,9, as well as prion transmission among other susceptible cervids.
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Acknowledgements
G.T. was supported by a fellowship from the Larry L. Hillblom Foundation. This work was supported by the Colorado Division of Wildlife and grants from the US Department of Defense National Prion Research Program (NP020152), the National Institutes of Health (AG02132) and the Hillblom Foundation. We thank P. Lessard and the staff of the Hunters Point animal facility for support with the transgenic animal experiments, K. Giles for screening transgenic animals, A. Serban for antibodies, K. Pomeroy for technical assistance, J. Safar for discussions, H. Nguyen for editorial assistance and B. Williams for insights on CWD transmission.
Author Contributions G.T., M.W.M. and S.B.P. designed the transgenic mouse studies; G.T., M.W.M., L.L.W., T.M.S., C.P., A.L. and S.J.D. performed various aspects of the research on mule deer or transgenic mice; G.T., M.W.M, D.V.G., S.J.D. and S.B.P. analysed the data; G.T., M.W.M., S.J.D. and S.B.P. wrote the paper. All authors discussed the results and commented on the manuscript.
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Tamgüney, G., Miller, M., Wolfe, L. et al. Asymptomatic deer excrete infectious prions in faeces. Nature 461, 529–532 (2009). https://doi.org/10.1038/nature08289
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DOI: https://doi.org/10.1038/nature08289
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