Viruses and interferon: a fight for supremacy

Nature Reviews Immunology volume 2, pages675–687(2002)Cite this article

Key Points

  • Interferons (IFNs) — the body's first line of antiviral defence — are cytokines that are secreted by host cells in response to virus infection. By inducing the expression of hundreds of IFN-stimulated genes, several of which have antiviral functions, IFNs block virus replication at many levels.

  • The global antiviral state of the cell involves cross-talk between IFN signalling and pathways that regulate apoptosis, inflammation and cellular stress-response programmes.

  • Viruses counteract the antiviral response by encoding mechanisms to control IFN signalling, block the actions of IFN-stimulated gene products and disrupt the various levels of cross-talk between IFNs and other cellular pathways. Studies of influenza virus, hepatitis C virus, herpes simplex virus and vaccinia virus highlight the importance of IFNs for the control of virus replication and pathogenesis.

  • Studies of both host antiviral pathways and viral-counteracting strategies will greatly benefit from the recent development of functional-genomic technologies, such as microarrays, proteomics and DNA shuffling. Our 'virus compendium' — a multi-faceted, functional genomics effort focusing in the field of virus–host interactions — will be useful to assimilate these data.

Abstract

The action of interferons (IFNs) on virus-infected cells and surrounding tissues elicits an antiviral state that is characterized by the expression and antiviral activity of IFN-stimulated genes. In turn, viruses encode mechanisms to counteract the host response and support efficient viral replication, thereby minimizing the therapeutic antiviral power of IFNs. In this review, we discuss the interplay between the IFN system and four medically important and challenging viruses — influenza, hepatitis C, herpes simplex and vaccinia — to highlight the diversity of viral strategies. Understanding the complex network of cellular antiviral processes and virus–host interactions should aid in identifying new and common targets for the therapeutic intervention of virus infection. This effort must take advantage of the recent developments in functional genomics, bioinformatics and other emerging technologies.

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Figure 1: Overview of the IFN pathway and viral-counteracting strategies.
Figure 2: Interplay between the type I IFN pathway and influenza virus.
Figure 3: Interplay between the type I IFN pathway and HCV.
Figure 4: Interplay between the type I IFN pathway and HSV.
Figure 5: Interplay between the IFN pathways and vaccinia virus.
Figure 6: The virus compendium.

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Acknowledgements

This work was supported by grants from the National Institutes of Health to M.G.K. and M.G. We thank M. J. Korth for editorial assistance and N.-W. Soong for helpful discussions.

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  1. Department of Microbiology, University of Washington, Seattle, 98195-8070, Washington, USA
    • Michael G. Katze
    •  & Yupeng He
  2. Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, 75390-9048, Texas, USA
    • Michael Gale Jr
  3. Antiviral Research, Abbott Laboratories, Abbott Park, 60064-6217, Illinois, USA
    • Yupeng He
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Glossary

NEGATIVE STRAND RNA GENOME

Genomic viral RNA that is complementary to the messenger RNA that is produced during infection.

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A family of closely related, but slightly different, viral genomes. Viral genetics variants, derived from the original infecting virus, that are present during an infection.

META-ANALYSIS

A large-scale comparison of NS5A sequences isolated from IFN-resistant or IFN-sensitive HIV-infected patients.

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Katze, M., He, Y. & Gale, M. Viruses and interferon: a fight for supremacy. Nat Rev Immunol 2, 675–687 (2002). https://doi.org/10.1038/nri888

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