Human
sporadic Creutzfeldt-Jakob disease (sCJD), endemic sheep
scrapie, and epidemic
bovine spongiform encephalopathy (BSE) are caused by a related group of infectious agents. The new U.K. BSE agent spread to many species, including humans, and clarifying the origin, specificity, virulence, and diversity of these agents is critical, particularly because infected humans do not develop disease for many years. As with viruses,
transmissible spongiform encephalopathy (TSE) agents can adapt to new species and become more virulent yet maintain fundamentally unique and stable identities. To make agent differences manifest, one must keep the host genotype constant. Many TSE agents have revealed their independent identities in normal mice. We transmitted primate
kuru, a TSE once epidemic in New Guinea, to mice expressing normal and approximately 8-fold higher levels of murine
prion protein (PrP). High levels of murine PrP did not prevent
infection but instead shortened incubation time, as would be expected for a viral receptor.
Sporadic CJD and BSE agents and representative
scrapie agents were clearly different from
kuru in incubation time, brain neuropathology, and lymphoreticular involvement. Many TSE agents can infect monotypic cultured GT1 cells, and unlike
sporadic CJD isolates,
kuru rapidly and stably infected these cells. The geographic independence of the
kuru agent provides additional reasons to explore causal environmental pathogens in these infectious
neurodegenerative diseases.