To replicate or not to replicate: achieving selective oncolytic virus replication in cancer cells through translational control

Abstract

To ensure that their mRNAs are translated and that the viral proteins necessary for assembling the next generation of infectious progeny are produced, viruses must effectively seize control of the translational machinery within their host cells. In many cases, the ability to productively engage host translational components can determine if a given cell type can support viral replication, illustrating the critical importance of this task in the viral life cycle. Failure to interface properly with the host translational apparatus can compromise the productive growth cycle, resulting in an abortive infection and radically restricting viral replication. Not only have viruses become facile at commandeering this machinery, they are also particularly adept at manipulating cellular translation control pathways for their own ends. In this review, the mechanisms by which numerous viruses manipulate host translational control circuits are discussed. Furthermore, particular attention is devoted to understanding how interfering with the ability of a virus to properly regulate translation in its host can be exploited to generate oncolytic strains that selectively replicate in cancer cells.