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Title:   Author  item
                                            COMOY, EMMANUEL - French Atomic Energy Commissionitem
                                            MIKOL, JACQUELINE - French Atomic Energy Commissionitem
                                            LUCCANTONI-FREIRE, SOPHIE - French Atomic Energy Commissionitem
                                            CORREIA, EVELYNE - French Atomic Energy Commissionitem
                                            LESCOUTRA-ETCHEGARAY, NATHALIE - French Atomic Energy Commissionitem
                                            DURAND, VALÉRIE - French Atomic Energy Commissionitem
                                            DEHEN, CAPUCINE - French Atomic Energy Commissionitem
                                            ANDREOLETTI, OLIVIER - Institut National De La Recherche Agronomique (INRA)item
                                            CASALONE, CRISTINA - Instituto Zooprofilattico Sperimentale Del Mazzogiornoitem
                                            Richt, Juergenitem
                                            Greenlee, Justinitem
                                            BARON, THIERRY - French Agency For Food, Environmental And Occupational Health & Safety (ANSES)item
                                            BENESTAD, SYLVIE - National Veterinary Institute - Norwayitem
                                            HILLS, BOB - Health Canadaitem
                                            BROWN, PAUL - French Atomic Energy Commissionitem
                                            DESLYS, JEAN-PHILIPPE - French Atomic Energy Commission
  Submitted to: Scientific Reports
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 5/28/2015
                                    Publication  Date: 6/30/2015
                                    Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C., Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J. 2015. Transmission of scrapie prions to primate after an extended silent incubation period. Scientific Reports. 5:11573.Interpretive Summary: The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed to feeds or foods contaminated with the disease agent. The purpose of this study was to test whether non-human primates (cynomologous macaque) are susceptible to the agent of sheep scrapie. After an incubation period of approximately 10 years a macaque developed progressive clinical signs suggestive of neurologic disease. Upon postmortem examination and microscopic examination of tissues, there was a widespread distribution of lesions consistent with a transmissible spongiform encephalopathy. This information will have a scientific impact since it is the first study that demonstrates the transmission of scrapie to a non-human primate with a close genetic relationship to humans. This information is especially useful to regulatory officials and those involved with risk assessment of the potential transmission of animal prion diseases to humans.
                                Technical Abstract: Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the past decades, c-BSE's zoonotic potential has been the driving force in establishing extensive protective measures for animal and human health. In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS. This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated. Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.


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