Translational regulation of viral RNA in the type I interferon response

Abstract The innate immune response serves as a robust first line of defense against pathogens, protecting the host from infectious organisms in a rapid and antigen-independent manner. Viral infection activates the type I interferon (IFN-I) response, leading to the production of hundreds of interferon-stimulated genes (ISGs). Many of these ISG-encoded proteins restrict viral infection by a variety of mechanisms that inhibit different stages of the virus life cycle. Translation inhibition, which restricts the production of viral proteins and host factors required for viral replication, is a common cellular response to viral infection. The IFN-I response induces translation inhibition primarily through the expression of ISG-encoded proteins. These proteins employ a variety of mechanisms to inhibit either global or virus-specific translation, resulting in restriction of viral replication and dissemination. In this graphical review, we provide an overview of the critical role of ISG-encoded proteins in translational regulation during the IFN-I response and viral infection. We focus on the molecular mechanisms by which ISG-encoded proteins restrict viral translation, including blocking the assembly of the translation machinery and inducing RNA degradation.