Evidence for zoonotic potential of ovine scrapie prions

• Published in: Nature communications Vol. 5; no. 1; p. 5821
• Main Authors: Cassard, Hervé, Torres, Juan-Maria, Lacroux, Caroline, Douet, Jean-Yves, Benestad, Sylvie L., Lantier, Frédéric, Lugan, Séverine, Lantier, Isabelle, Costes, Pierrette, Aron, Naima, Reine, Fabienne, Herzog, Laetitia, Espinosa, Juan-Carlos, Beringue, Vincent, Andréoletti, Olivier
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-12-2014; Nature Publishing Group
• Subjects: 13; 631/80/470/460; 64; 64/60; 692/308; 692/699/375/365/1937; 692/700/478/174; 82; 82/1; Animals; Brain - metabolism; Brain - pathology; Cattle; Creutzfeldt-Jakob Syndrome - pathology; Creutzfeldt-Jakob Syndrome - transmission; Encephalopathy, Bovine Spongiform - pathology; Encephalopathy, Bovine Spongiform - transmission; Female; Humanities and Social Sciences; Humans; Life Sciences; Mice; Mice, Transgenic; Microbiology and Parasitology; multidisciplinary; Other; Prions - chemistry; Prions - genetics; Prions - metabolism; Science; Science (multidisciplinary); Scrapie - pathology; Scrapie - transmission; Sheep; Zoonoses - pathology; Zoonoses - transmission
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms6821

Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
Scrapie, a form of prion disease that affects sheep and goats, is believed not to be transmissible to humans. Using transgenic mice expressing human prion protein as a model of cross-species prion transmission, the authors show that ovine scrapie may possess potential to be passed on to humans.