The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5 and inhibit its activation of the IFN-β promoter

J Andrejeva, KS Childs, DF Young, TS Carlos, N Stock, S Goodbourn, Richard Edward Randall

Research output: Contribution to journalArticlepeer-review

844 Citations (Scopus)

Abstract

Most paramyxoviruses circumvent the IFN response by blocking IFN signaling and limiting the production of IFN by virus-infected cells. Here we report that the highly conserved cysteine-rich C-terminal domain of the V proteins of a wide variety of paramyxoviruses binds melanoma differentiation-associated gene 5 (mda-5) product. mda-5 is an IFN-inducible host cell DExD/H box helicase that contains a caspase recruitment domain at its N terminus. Overexpression of mda-5 stimulated the basal activity of the IFN-beta promoter in reporter gene assays and significantly enhanced the activation of the IFN-beta promoter by intracellular dsRNA. Both these activities were repressed by coexpression of the V proteins of simian virus 5, human parainfluenza virus 2, mumps virus, Sendai virus, and Hendra virus. Similar results to the reporter assays were obtained by measuring IFN production. inhibition of mda-5 by RNA interference or by dominant interfering forms of mda-5 significantly inhibited the activation of the IFN-beta promoter by dsRNA. It thus appears that mda-5 plays a central role in an intracellular signal transduction pathway that can lead to the activation of the IFN-beta promoter, and that the V proteins of paramyxoviruses interact with mda-5 to block its activity.

Original languageEnglish
Pages (from-to)17264-17269
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number49
DOIs
Publication statusPublished - 7 Dec 2004

Keywords

  • interferon
  • NF-kappa B
  • innate immunity
  • INTERFERON ANTIVIRAL RESPONSE
  • MAMMALIAN-CELLS
  • I INTERFERON
  • SIMIAN-VIRUS-5
  • DEGRADATION
  • APOPTOSIS
  • VIRUSES
  • STAT1
  • EXPRESSION
  • COMPONENTS

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