Multifaceted Antiviral Actions of Interferon-stimulated Gene Products

Strobl, Birgit; Leitner, Nicole R.; Müller, Mathias

Interferons (IFNs) are extremely powerful cytokines for the host defence against viral infections. Binding of IFNs to their receptors activates the JAK/STAT signalling pathway with the Janus kinases JAK1, 2 and TYK2 and the signal transducer and activators of transcription (STAT) 1 and STAT2. Depending on the cellular setting, additional STATs (STAT3-6) and additional signalling pathways are activated. The actions of IFNs on infected cells and the surrounding tissue are mediated by the induction of several hundred IFN-stimulated genes (ISGs). Since the cloning of the first ISGs, considerable progress has been made in describing antiviral effector proteins and their many modes of action. Effector proteins individually target distinct steps in the viral life cycle, including blocking virus entry, inhibition of viral transcription and translation, modification of viral nucleic acids and proteins and, interference with virus assembly and budding. Novel pathways of viral inhibition are constantly being elucidated and, additionally, unanticipated functions of known antiviral effector proteins are discovered. Herein, we outline IFN-induced antiviral pathways and review recent developments in this fascinating area of research.