Full restoration of specific infectivity and strain properties from pure mammalian prion protein
Fig 7
Unified model of mammalian prion infectivity.
Proposed model of prion infectivity, in which the global structure of protein-only PrPSc (formed in reaction I lacking cofactor molecules) can store latent information, but local conformational changes caused by the absence of cofactor abrogates infectivity. The local changes can be repaired by sPMCA in substrate containing BV PrPC and cofactors (reaction II), immediately restoring full specific infectivity. Despite the temporary loss of infectivity, the two-step process (reactions I + II) recovers a prion strain that possesses full specific infectivity and is clinically, biochemically, and pathologically indistinguishable from BV cofactor recPrPSc, in which the specific infectivity of the parental seed was continuously maintained by propagation in the presence of cofactor molecules (reaction III). Non-infectious, protein-only samples are shown in blue, and infectious samples produced with cofactor are shown in red.