Transcriptional Regulation of Antiviral Interferon-Stimulated Genes

Interferon-stimulated genes (ISGs) are a group of gene products that coordinately combat pathogen invasions, in particular viral infections. Transcription of ISGs occurs rapidly upon pathogen invasion, and this is classically provoked via activation of the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway, mainly by interferons (IFNs). However, a plethora of recent studies have reported a variety of non-canonical mechanisms regulating ISG transcription. These new studies are extremely important for understanding the quantitative and temporal differences in ISG transcription under specific circumstances. Because these canonical and non-canonical regulatory mechanisms are essential for defining the nature of host defense and associated detrimental proinflammatory effects, we comprehensively review the state of this rapidly evolving field and the clinical implications of recently acquired knowledge in this respect. Transcriptional regulation of ISGs defines the state of host anti-pathogen defense.In light of the recently identified regulatory elements and mechanisms of the IFN-JAK-STAT pathway, new insights have been gained into this classical cascade in regulating ISG transcription.A variety of non-canonical mechanisms have been recently revealed that coordinately regulate ISG transcription.With regards to the adverse effects of IFNs in clinic, ISG-based antiviral strategy could be the next promising frontier in drug discovery.

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