Assessment of the Zoonotic Potential of Atypical Scrapie Prions in Humanized Mice Reveals Rare Phenotypic Convergence but Not Identity With Sporadic Creutzfeldt-Jakob Disease Prions.

This article focuses on assessing the zoonotic potential of atypical/Nor98 scrapie (AS), an idiopathic prion disease affecting sheep and goats, by experimentally inoculating AS isolates into transgenic mice overexpressing the human prion protein (PrP) Met129 allele. The study found no clinical disease or prion accumulation on primary passage, indicating a strong species barrier; however, one AS isolate adapted on subsequent passages, producing prions phenotypically resembling MM1-type sporadic Creutzfeldt-Jakob disease (sCJD) in humans, though further analyses confirmed these as distinct strains exhibiting phenotypic convergence. Importantly, no classical bovine spongiform encephalopathy (C-BSE) prions emerged in the humanized mice, including in spleen tissue, which is typically permissive to C-BSE transmission. These findings suggest a low risk of AS transmission to humans but highlight the potential for rare prion adaptations that mimic spontaneous human prion diseases, underscoring the need for continued surveillance and strain-specific diagnostic approaches.