title: PrP(Sc) of scrapie 263K propagates efficiently in spleen and muscle tissues with protein misfolding cyclic amplification.
abstract: Transmissible spongiform encephalopathies (TSEs), or prion diseases, are transmissible neurodegenerative disorders of protein conformation. This group of diseases is caused by infectious agents, termed prions, which can convert normal conformation (PrP(C)) into misfolded protein (PrP(Sc)). The infectivity of non-neuronal tissues has been wildly addressed, but the propagating features and the biochemical properties of prion generated from these tissues are only partially settled. In this study, utilizing protein misfolding cyclic amplification (PMCA), the in vitro conversion of PrP(C) into PrP(Sc) in spleen and muscle tissues can be induced by PrP(Sc) produced in vivo. The further propagation of newly formed PrP(Sc) in normal brain and some of the biochemical properties of new PrP(Sc) are similar as the brain-derived prions, implying the naturally infectious pathway of prion from peripheral generation to neuro-invasion. However, compared with the brain-derived PrP(Sc), the weaker resistance of new PrP(Sc) to some inactivated agents, i.e. sodium hydroxide and thermal inactivation, are observed. Our data provide the reliable evidence that the brain-derived PrP(Sc) can utilize the PrP(C) from non-neuronal tissues for its propagation. Similarity of the replicative ability in PMCA in vitro and the infectivity in vivo highlights the possibility to use PMCA instead of bioassay to investigate the propagation of prion.
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Ying-Xin Rd 100, Beijing 100052, People's Republic of China.
authors.forename: Song
authors.initials: S
authors.lastname: Shi
authors.forename: Chen-Fang
authors.initials: CF
authors.lastname: Dong
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Run
authors.initials: R
authors.lastname: An
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Shan
authors.forename: Bao-Yun
authors.initials: BY
authors.lastname: Zhang
authors.forename: Kun
authors.initials: K
authors.lastname: Xu
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.forename: Chan
authors.initials: C
authors.lastname: Tian
authors.forename: Chen
authors.initials: C
authors.lastname: Gao
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Dong
mesh_terms: D000818:Animals; D006224:Cricetinae; D006801:Humans; D009132:Muscles / Q000737:chemistry / Q000378:metabolism*; D018621:PrPC Proteins / Q000737:chemistry / Q000378:metabolism; D018620:PrPSc Proteins / Q000737:chemistry* / Q000378:metabolism*; D017510:Protein Folding; D012608:Scrapie / Q000378:metabolism*; D013154:Spleen / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018621:PrPC Proteins; D018620:PrPSc Proteins