A diverse range of gene products are effectors of the type i interferon antiviral response

John W. Schoggins, Sam J. Wilson, Maryline Panis, Mary Y. Murphy, Christopher T. Jones, Paul Bieniasz, Charles M. Rice

Research output: Contribution to journalArticle

1105 Citations (Scopus)

Abstract

The type I interferon response protects cells against invading viral pathogens. The cellular factors that mediate this defence are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified since their discovery more than 25 years ago, only a few have been characterized with respect to antiviral activity. For most ISG products, little is known about their antiviral potential, their target specificity and their mechanisms of action. Using an overexpression screening approach, here we show that different viruses are targeted by unique sets of ISGs. We find that each viral species is susceptible to multiple antiviral genes, which together encompass a range of inhibitory activities. To conduct the screen, more than 380 human ISGs were tested for their ability to inhibit the replication of several important human and animal viruses, including hepatitis C virus, yellow fever virus, West Nile virus, chikungunya virus, Venezuelan equine encephalitis virus and human immunodeficiency virus type-1. Broadly acting effectors included IRF1, C6orf150 (also known as MB21D1), HPSE, RIG-I (also known as DDX58), MDA5 (also known as IFIH1) and IFITM3, whereas more targeted antiviral specificity was observed with DDX60, IFI44L, IFI6, IFITM2, MAP3K14, MOV10, NAMPT (also known as PBEF1), OASL, RTP4, TREX1 and UNC84B (also known as SUN2). Combined expression of pairs of ISGs showed additive antiviral effects similar to those of moderate type I interferon doses. Mechanistic studies uncovered a common theme of translational inhibition for numerous effectors. Several ISGs, including ADAR, FAM46C, LY6E and MCOLN2, enhanced the replication of certain viruses, highlighting another layer of complexity in the highly pleiotropic type I interferon system.

Original languageEnglish (US)
Pages (from-to)481-485
Number of pages5
JournalNature
Volume472
Issue number7344
DOIs
StatePublished - Apr 28 2011

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Interferons
Antiviral Agents
Interferon Type I
Genes
Venezuelan Equine Encephalitis Viruses
Chikungunya virus
Yellow fever virus
Viruses
West Nile virus
Virus Replication
Hepacivirus
HIV-1

ASJC Scopus subject areas

  • General

Cite this

Schoggins, J. W., Wilson, S. J., Panis, M., Murphy, M. Y., Jones, C. T., Bieniasz, P., & Rice, C. M. (2011). A diverse range of gene products are effectors of the type i interferon antiviral response. Nature, 472(7344), 481-485. https://doi.org/10.1038/nature09907

A diverse range of gene products are effectors of the type i interferon antiviral response. / Schoggins, John W.; Wilson, Sam J.; Panis, Maryline; Murphy, Mary Y.; Jones, Christopher T.; Bieniasz, Paul; Rice, Charles M.

In: Nature, Vol. 472, No. 7344, 28.04.2011, p. 481-485.

Research output: Contribution to journalArticle

Schoggins, JW, Wilson, SJ, Panis, M, Murphy, MY, Jones, CT, Bieniasz, P & Rice, CM 2011, 'A diverse range of gene products are effectors of the type i interferon antiviral response', Nature, vol. 472, no. 7344, pp. 481-485. https://doi.org/10.1038/nature09907
Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P et al. A diverse range of gene products are effectors of the type i interferon antiviral response. Nature. 2011 Apr 28;472(7344):481-485. https://doi.org/10.1038/nature09907
Schoggins, John W. ; Wilson, Sam J. ; Panis, Maryline ; Murphy, Mary Y. ; Jones, Christopher T. ; Bieniasz, Paul ; Rice, Charles M. / A diverse range of gene products are effectors of the type i interferon antiviral response. In: Nature. 2011 ; Vol. 472, No. 7344. pp. 481-485.
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