Interferon-inducible antiviral effectors

Key Points

• Interferons (IFNs) are key components of the innate immune response and the first line of defence against virus infection.

• Among the hundreds of IFN-induced genes, only a few have been ascribed direct antiviral activity in vivo: ISG15 (IFN-stimulated protein of 15 kDa), the Mx (myxovirus resistance) proteins, 2′,5′-oligoadenylate synthetase (OAS)-regulated ribonuclease L (RNaseL) and protein kinase R (PKR).

• These proteins separately block viral transcription, degrade viral RNA, inhibit translation or modify the proteasome to control all steps of viral replication.

• ISG15 is part of a ubiquitin-like pathway that modulates the function of numerous protein targets.

• The Mx proteins seem to survey exocytic events and mediate vesicle trafficking to trap viral components.

• The OAS-regulated RNaseL pathway degrades single-stranded RNA in virus-infected cells.

• PKR inhibits translation and participates in signal transduction.

• Additional functions of each of these proteins are still being uncovered, suggesting they have broader roles in the host immune response.

Abstract

Type I interferons (IFNs) provide the first line of defence against viral infection. As discussed in this Review, the IFN-induced antiviral effector proteins, such as ISG15, Mx proteins, ribonuclease L and protein kinase R, are important components of this response.

Abstract

Since the discovery of interferons (IFNs), considerable progress has been made in describing the nature of the cytokines themselves, the signalling components that direct the cell response and their antiviral activities. Gene targeting studies have distinguished four main effector pathways of the IFN-mediated antiviral response: the Mx GTPase pathway, the 2′,5′-oligoadenylate-synthetase-directed ribonuclease L pathway, the protein kinase R pathway and the ISG15 ubiquitin-like pathway. As discussed in this Review, these effector pathways individually block viral transcription, degrade viral RNA, inhibit translation and modify protein function to control all steps of viral replication. Ongoing research continues to expose additional activities for these effector proteins and has revealed unanticipated functions of the antiviral response.