The
prion hypothesis postulates that the infectious agent in
transmissible spongiform encephalopathies (TSEs) is an unorthodox protein conformation based agent. Recent successes in generating mammalian
prions in vitro with bacterially expressed recombinant
prion protein provide strong support for the hypothesis. However, whether the pathogenic properties of synthetically generated
prion (rec-
Prion) recapitulate those of naturally occurring
prions remains unresolved. Using end-point titration assay, we showed that the in vitro prepared rec-
Prions have infectious titers of around 104 LD50/μg. In addition, intraperitoneal (i.p.) inoculation of wild-type mice with rec-
Prion caused
prion disease with an average survival time of 210-220 days post inoculation. Detailed pathological analyses revealed that the nature of rec-
Prion induced lesions, including spongiform change, disease specific
prion protein accumulation (
PrP-d) and the
PrP-d dissemination amongst lymphoid and peripheral nervous system tissues, the route and mechanisms of neuroinvasion were all typical of classical rodent
prions. Our results revealed that, similar to naturally occurring
prions, the rec-
Prion has a titratable infectivity and is capable of causing
prion disease via routes other than direct intra-cerebral challenge. More importantly, our results established that the rec-
Prion caused disease is pathogenically and pathologically identical to naturally occurring contagious TSEs, supporting the concept that a conformationally altered
protein agent is responsible for the infectivity in TSEs.