PRNP and human prion disease: Several factors may participate in the transmission of the inoculated TSE agent when three different PrP amino acid sequences are implicated: (i) the transmission barrier of each PrPC to the inoculated PrPSc, (ii) the differential ability of each PrPC to replicate the inoculated prion strain, and (iii) the interference effect of each PrPC on the replication of the other.