20 Protein Synthesis and Translational Control during Viral Infection

Abstract

Viruses are obligate intracellular parasites or symbionts and depend on cells for their replication. Nowhere is this dependency seen more clearly than in the translation system, as viruses—unlike cells and their endosymbiotic organelles, chloroplasts and mitochondria—lack a translational apparatus. Consequently, viruses must use the cellular apparatus for the synthesis of one of their principal components. Because they can be manipulated with relative ease, the study of viruses has been a pre-eminent source of information on the mechanism and regulation of the protein synthetic machinery (Table 1). Viruses do more than simply co-opt the cellular machinery to produce viral proteins, however. Under extreme selection pressure, many viruses have evolved ways to gain a translational advantage for their mRNAs and to contend with potent host defense systems that affect protein synthesis. Here we consider the interactions between viruses and the translation system of the cell under three headings: Translational mechanisms. Viruses exploit a range of unorthodox mechanisms, most of which were discovered in viral systems. Many of them have proven to be used in the uninfected cell, albeit seemingly less frequently or in special circumstances such as during apoptosis or in response to environmental stress. Modifications of the translation system. Many viruses impose sweeping changes upon the cellular translation machinery and the signaling network that regulates it, modifying these systems to favor the synthesis of viral proteins at the cells’ expense. Host defenses and viral countermeasures. Host defenses impinge on translation at many levels, from direct effects...