Cell biology of prion infection.

The development of multiple cell culture models of prion infection over the last two decades has led to a significant increase in our understanding of how prions infect cells. In particular, new techniques to distinguish exogenous from endogenous prions have allowed us for the first time to look in depth at the earliest stages of prion infection through to the establishment of persistent infection. These studies have shown that prions can infect multiple cell types, both neuronal and nonneuronal. Once in contact with the cell, they are rapidly taken up via multiple endocytic pathways. After uptake, the initial replication of prions occurs almost immediately on the plasma membrane and within multiple endocytic compartments. Following this acute stage of prion replication, persistent prion infection may or may not be established. Establishment of a persistent prion infection in cells appears to depend upon the achievement of a delicate balance between the rate of prion replication and degradation, the rate of cell division, and the efficiency of prion spread from cell to cell. Overall, cell culture models have shown that prion infection of the cell is a complex and variable process which can involve multiple cellular pathways and compartments even within a single cell. 2018 Published by Elsevier B.V.