Direct Cleavage, Proteasomal Degradation and Sequestration: Three Mechanisms of Viral Subversion of Type I Interferon Responses

The host type I interferon (IFN) system is central in antiviral defence and represents one of the greatest obstacles for a virus to overcome in order to establish a productive infection. Viruses have evolved many different mechanisms to repress the effects of the type I IFN system. For example, a number of viruses encode viral proteases, which can directly cleave and inactivate key components of the type I IFN induction and signalling pathway. Others recruit the ubiquitin proteasome system to destabilise proteins that are important for IFN responses. There are also many known viral proteins, which bind to and sequester proteins of the type I IFN system in an inactive state. Here, we review each of these different mechanisms of viral escape from the type I IFN response with examples from a range of viruses.