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Multifaceted Antiviral Actions of Interferon-stimulated Gene Products

  • Birgit Strobl
  • Nicole R. Leitner
  • Mathias Müller
Chapter

Abstract

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.

Keywords

Antiviral Activity West Nile Virus Vesicular Stomatitis Virus Mouse Mammary Tumour Virus Hepatitis Delta Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

For virus abbreviations see Table 2

ADAR

Adenosine deaminase acting on RNA

APOBEC

Apolipoprotein B mRNA-editing catalytic polypeptide

BST-2

Bone marrow stromal antigen 2

ds

Double-stranded

eIF

Eukaryotic translation initiation factor

ER

Endoplasmatic reticulum

GAS

IFNγ activated sequence

GBP

Guanylate binding protein

IFN

Interferon

IFNAR

IFNα/β receptor

IL

Interleukin

ISG

IFN-stimulated gene

IFIT

IFN-induced protein with tetratricopeptide repeats

IFITM

IFN-induced transmembrane protein

ISGF3

IFN-stimulated gene factor 3

IRF

IFN regulatory factor

ISRE

IFN-stimulated response element

JAK

Janus kinase

PML

Promyelocytic leukaemia

2-5An

2′-5′ oligoadenylate

OAS

2-5An synthetase

MDA5

Melanoma differentiation-associated protein 5

PAMP

Pathogen-associated molecular pattern

PKR

dsRNA-dependent protein kinase

PRR

Pattern-recognition receptor

RIG-I

Retinoic acid-inducible protein I

RNase L

Latent ribonuclease

ss

Single-stranded

STAT

Signal transducer and activator of transcription

TRIM

Tripartite motif

TYK2

Tyrosine kinase 2

Notes

Acknowledgements

We apologize for not citing work of authors who made important contributions to the field of interferons and antiviral effector proteins. Due to space limitations we were unable to include as many primary publications as we would have liked, instead we refer to a number of excellent reviews. We are grateful to Rita Stiefvater and Caroline Lassnig for critically reading the manuscript. MM and BS are supported by the Austrian Science fund (FWF SFB-28) and GEN-AU III (“Inflammobiota”) and MM and NL by GEN-AU II/III (“Austrian Network for Functional Genomics of the Mouse”). MM is further supported by the Austrian Federal Ministry for Science and Research (GZ.200.191/1-II/1a/2008 to Biomodels Austria).

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Copyright information

© Springer-Verlag Wien 2012

Authors and Affiliations

  • Birgit Strobl
    • 1
  • Nicole R. Leitner
    • 1
  • Mathias Müller
    • 1
    • 2
  1. 1.Institute of Animal Breeding and GeneticsUniversity of Veterinary Medicine ViennaViennaAustria
  2. 2.Biomodels AustriaUniversity of Veterinary Medicine ViennaViennaAustria

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