Animal prion strains around the globe

Prion diseases including scrapie in sheep, Bovine Spongiform Encephalopathy (BSE) in cattle and Chronic Wasting Disease (CWD) in cervids are caused by the conversion of the host-encoded prion protein into a pathologic isoform (PrP^Sc). Moreover, classical PrP^Sc occur as different prion strains that determine disease phenotypes. To unravel the global diversity of prion strains, an in-depth characterization of animal prion isolates was performed, using the transgenic ovinized Tgshp IX mouse model (ARQ-genotype), which also allow to evaluate the interspecies transmission potential of the BSE and CWD isolates. The PrP^Sc-profile obtained after intracerebral inoculation of atypical and classical BSE, European and Canadian goat and Libyan sheep scrapie as well as Canadian and European CWD isolates was comparatively analysed.

Classical BSE presented itself highly zoonotic, while the transmission of the atypical BSE and CWD isolates remained incomplete. Nevertheless, isolates of H- and L-type BSE, Canadian elk, moose, red deer and two Swedish moose isolates transmitted after first passage as did all scrapie isolates. The histopathological lesion profile of all isolates predicted severe PrP^Sc accumulation, but it is insufficient for strain-typing. However, the immunohistochemical PrP^Sc profile of the corpus callosum and cerebellum in particular enabled a clear-cut discrimination to be made between different prion strains in the isolates used.

The Tgshp IX mouse model provides reliable data for prion strain discrimination, revealing the diversity of prion strains circulating around the globe. This model also indicates that certain CWD isolates as well as atypical BSE might pose a threat to small ruminants.