Regulation Mechanisms of Viral IRES-Driven Translation

For efficient viral IRES-dependent translation and rapid adaption, RNA viruses redistribute IRES trans-acting factors (ITAFs) by either forcing leakage from the nucleus, or cleaving the NLS, and the cleavage of eIF4G and ITAFs by viral proteases is a critical mechanism of RNA viruses to regulate IRES-dependent translation Post-translational modification of ITAFs represents alternative strategies for viruses to utilize cellular resources for better fitness. Elucidation of viral IRES-mediated translation not only helps the development of antiviral strategies, but also provides an opportunity for the therapeutic application of genetically modified viruses, such as an oncolytic virus. Internal ribosome entry sites (IRESs) can be found in the mRNA of many viruses as well as in cellular genes involved in the stress response, cell cycle, and apoptosis. IRES-mediated translation can occur when dominant cap-dependent translation is inhibited, and viruses can take advantage of this to subvert host translation machinery. In this review, we focus on the four major types of IRES identified in RNA viruses, and outline their distinct structural properties and requirements of translational factors. We further discuss auxiliary host factors known as IRES trans-acting factors (ITAFs), which are involved in the modulation of optimal IRES activity. Currently known strategies employed by viruses to harness ITAFs and regulate IRES activity are also highlighted. Internal ribosome entry sites (IRESs) can be found in the mRNA of many viruses as well as in cellular genes involved in the stress response, cell cycle, and apoptosis. IRES-mediated translation can occur when dominant cap-dependent translation is inhibited, and viruses can take advantage of this to subvert host translation machinery. In this review, we focus on the four major types of IRES identified in RNA viruses, and outline their distinct structural properties and requirements of translational factors. We further discuss auxiliary host factors known as IRES trans-acting factors (ITAFs), which are involved in the modulation of optimal IRES activity. Currently known strategies employed by viruses to harness ITAFs and regulate IRES activity are also highlighted.