Species-barrier-independent prion replication in apparently resistant species.
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.
Hill
A F
AF
Medical Research Council Prion Unit and Department of Neurogenetics, Imperial College School of Medicine at St. Mary's, London W2 1PG, United Kingdom.
Joiner
S
S
Linehan
J
J
Desbruslais
M
M
Lantos
P L
PL
Collinge
J
J
D000818:Animals; D001921:Brain / Q000473:pathology*; D002417:Cattle; D006224:Cricetinae; D006801:Humans; D008647:Mesocricetus; D051379:Mice; D018620:PrPSc Proteins / Q000032:analysis*; D017096:Prion Diseases / Q000473:pathology / Q000635:transmission*; D012608:Scrapie / Q000473:pathology / Q000635:transmission*; D013045:Species Specificity
D018620:PrPSc Proteins