title: Infectivity-associated PrP(Sc) and disease duration-associated PrP(Sc) of mouse BSE prions.
abstract: Disease-related prion protein (PrP(Sc)), which is a structural isoform of the host-encoded cellular prion protein, is thought to be a causative agent of transmissible spongiform encephalopathies. However, the specific role of PrP(Sc) in prion pathogenesis and its relationship to infectivity remain controversial. A time-course study of prion-affected mice was conducted, which showed that the prion infectivity was not simply proportional to the amount of PrP(Sc) in the brain. Centrifugation (20,000 ×g) of the brain homogenate showed that most of the PrP(Sc) was precipitated into the pellet, and the supernatant contained only a slight amount of PrP(Sc). Interestingly, mice inoculated with the obtained supernatant showed incubation periods that were approximately 15 d longer than those of mice inoculated with the crude homogenate even though both inocula contained almost the same infectivity. Our results suggest that a small population of fine PrP(Sc) may be responsible for prion infectivity and that large, aggregated PrP(Sc) may contribute to determining prion disease duration.
authors.affiliation: a Influenza and Prion Disease Research Center; National Institute of Animal Health ; Tsukuba , Ibaraki , Japan.
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Miyazawa
authors.affiliation: a Influenza and Prion Disease Research Center; National Institute of Animal Health ; Tsukuba , Ibaraki , Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okada
authors.affiliation: a Influenza and Prion Disease Research Center; National Institute of Animal Health ; Tsukuba , Ibaraki , Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Masujin
authors.affiliation: a Influenza and Prion Disease Research Center; National Institute of Animal Health ; Tsukuba , Ibaraki , Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Iwamaru
authors.affiliation: a Influenza and Prion Disease Research Center; National Institute of Animal Health ; Tsukuba , Ibaraki , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D051379:Mice; D018620:PrPSc Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*
chemical_list: D018620:PrPSc Proteins; D011328:Prions
keywords: PK-digestion; PrPSc aggregation; endpoint titration; incubation period; prion infectivity