Species-barrier-independent prion replication in apparently resistant species

TLDR

Prion transmission between mammalian species is limited by a species barrier that depends on differences in the primary structure of prion proteins in the inoculum and host. Current definitions of the species barrier, based on clinical endpoints, must be fundamentally reassessed. We show that hamster prions previously considered nonpathogenic can replicate to high levels in mice without clinical disease, produce prions pathogenic to both species, and reveal subclinical infections with significant public health implications for iatrogenic and dietary exposure.

Abstract

Transmission of prions between mammalian species is thought to be limited by a “species barrier,” which depends on differences in the primary structure of prion proteins in the infecting inoculum and the host. Here we demonstrate that a strain of hamster prions thought to be nonpathogenic for conventional mice leads to prion replication to high levels in such mice but without causing clinical disease. Prions pathogenic in both mice and hamsters are produced. These results demonstrate the existence of subclinical forms of prion infection with important public health implications, both with respect to iatrogenic transmission from apparently healthy humans and dietary exposure to cattle and other species exposed to bovine spongiform encephalopathy prions. Current definitions of the species barrier, which have been based on clinical end-points, need to be fundamentally reassessed.