Mechanism of mda-5 Inhibition by paramyxovirus V proteins

K S Childs, Jelena Andrejeva, Richard Edward Randall, S Goodbourn

Research output: Contribution to journalArticlepeer-review

108 Citations (Scopus)

Abstract

The RNA helicases encoded by melanoma differentiation-associated gene 5 (mda-5) and retinoic acid-inducible gene I (RIG-I) detect foreign cytoplasmic RNA molecules generated during the course of a virus infection, and their activation leads to induction of type I interferon synthesis. Paramyxoviruses limit the amount of interferon produced by infected cells through the action of their V protein, which binds to and inhibits mda-5. Here we show that activation of both mda-5 and RIG-I by double-stranded RNA (dsRNA) leads to the formation of homo-oligomers through self-association of the helicase domains. We identify a region within the helicase domain of mda-5 that is targeted by all paramyxovirus V proteins and demonstrate that they inhibit activation of mda-5 by blocking dsRNA binding and consequent self-association. In addition to this commonly targeted domain, some paramyxovirus V proteins target additional regions of mda-5. In contrast, V proteins cannot bind to RIG-I and consequently have no effect on the ability of RIG-I to bind dsRNA or to form oligomers.

Original languageEnglish
Pages (from-to)1465-1473
Number of pages9
JournalJournal of Virology
Volume83
Issue number3
Early online date19 Nov 2008
DOIs
Publication statusPublished - Feb 2009

Keywords

  • INDUCIBLE GENE-I
  • SIMIAN-VIRUS 5
  • RIG-I
  • INTERFERON-BETA
  • ANTIVIRAL RESPONSES
  • RNA VIRUSES
  • INNATE IMMUNITY
  • ACTIVATION
  • RECOGNITION
  • INDUCTION

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