Ubiquitin as a regulator of IFN production in the antiviral response

Abstract

Type I interferons (IFNs) are important in the immune response. After pathogen detection, host cells rapidly trigger innate immune mechanisms such as inflammatory cytokines production, thus leading to the eradication of the invading virus. Such mechanisms engage signaling cascades which, in the initial phase of infection, lead to the activation of the NF-κB pathway and IFN regulatory factors (IRF-3, IRF-7) which directly control the production of IFNs. Proper regulation of IFN induction takes place by ubiqutination and allows to maintain a balance between the activation and inhibition of the immune system response due to an infection. Studies in recent years indicate that ubiquitination of proteins can affect both proteasomal degradation as well as the non-canonical pathway which results in the regulation of their activity. The type of ubiquitination primarily depends on the attachment of ubiquitin chain to thetarget protein but also on the activity of proteases from DUBs family. The ubiquitin pathway holds many potential therapeutic targets. Thus, the more detailed understanding of the mechanism of ubiquitination and the role of ubiquitin involved in IFNs production pathways may provide a turning point for both antiviral therapy and autoimmune diseases.