Zoonotic potential of ruminant prion diseases: from primate to mice

Introduction: previous experiments reported the transmission of certain isolates of sheep scrapie to humanized mice and non-human primates, supporting an unexpected zoonotic potential of an animal disease known from centuries. For some of them, transmission to rodents were observed only after an intermediate passage in transgenic mice expressing bovine PrP (Tg110), this sequential transmission being considered as a model of the hypothesis of a scrapie origin of BSE.

Objectives: we aim to complete this second part of experiments in our non-human primate model that is known as sensitive to human and cattle prion strains.

Methods: cynomolgus macaques were intracerebrally exposed to different scrapie isolates directly issued from sheep or after passages in Tg110 transgenic mice, and post mortem analysed using conventional biochemical and histological techniques. Successive transmissions to mice expressing ovine, bovine or macaque PrP were performed.

Results/Discussion: These new macaque studies confirmed that scrapie can be transmitted from certain sheep isolates to non-human primate after extended incubation periods (10 years), whereas after passage in Tg110 mice transmission may occur with two-fold shorter incubation periods. These resulting diseases and BSE will be compared according to their respective biochemical, pathological and transmission features. The combined observation of unexpected immunohistological labelling with reverse yet unpublished experiments of BSE passage on small ruminants as intermediate hosts, underline the impact of the host species on the phenotype and the zoonotic potential of animal prion diseases, enforcing the pivotal role played by cattle.