4 Transmission and Replication of Prions

Abstract

INTRODUCTION
One of the most remarkable features of slow infections is the clock-work precision with which the replication of prions occurs. Inoculation of numerous animals with the same dose of prions results in the onset of illness at the same time many months later. The molecular mechanisms controlling this extraordinarily precise process are unknown.

The term “infection” implies that a pathogen replicates during this process. When the infectious pathogen has achieved a high titer, a disease in the host generally appears. Prior to the recognition of the existence of prions, all infectious pathogens contained a nucleic acid genome that encoded their progeny. Copying of this genome by a polynucleotide polymerase provided a means of replicating the pathogen; in the case of prions, which lack nucleic acid, another mechanism clearly functions.

General Features of Prion Transmission and Replication
As we learn more about prions, some general features and rules of prion replication are beginning to emerge. Although many of the results described here can be found in other chapters, the consolidation of data on prion transmission and replication in this chapter is important.

Prion replication requires the prion protein (PrP); specifically, interaction between the central regions of its normal, cellular isoform (PrP^C) and its aberrantly folded isoform (PrP^Sc) (Prusiner et al. 1990; Scott et al. 1993). This process can replicate many different PrP^Sc conformations since prion strains breed true (Telling et al. 1996; Scott et al. 1999; Peretz et al. 2002). Amino acid substitutions modulate the rate of prion replication: In...