Processing of genome 5' termini as a strategy of negative-strand RNA viruses to avoid RIG-I-dependent interferon induction

PLoS One. 2008 Apr 30;3(4):e2032. doi: 10.1371/journal.pone.0002032.

Abstract

Innate immunity is critically dependent on the rapid production of interferon in response to intruding viruses. The intracellular pathogen recognition receptors RIG-I and MDA5 are essential for interferon induction by viral RNAs containing 5' triphosphates or double-stranded structures, respectively. Viruses with a negative-stranded RNA genome are an important group of pathogens causing emerging and re-emerging diseases. We investigated the ability of genomic RNAs from substantial representatives of this virus group to induce interferon via RIG-I or MDA5. RNAs isolated from particles of Ebola virus, Nipah virus, Lassa virus, and Rift Valley fever virus strongly activated the interferon-beta promoter. Knockdown experiments demonstrated that interferon induction depended on RIG-I, but not MDA5, and phosphatase treatment revealed a requirement for the RNA 5' triphosphate group. In contrast, genomic RNAs of Hantaan virus, Crimean-Congo hemorrhagic fever virus and Borna disease virus did not trigger interferon induction. Sensitivity of these RNAs to a 5' monophosphate-specific exonuclease indicates that the RIG-I-activating 5' triphosphate group was removed post-transcriptionally by a viral function. Consequently, RIG-I is unable to bind the RNAs of Hantaan virus, Crimean-Congo hemorrhagic fever virus and Borna disease virus. These results establish RIG-I as a major intracellular recognition receptor for the genome of most negative-strand RNA viruses and define the cleavage of triphosphates at the RNA 5' end as a strategy of viruses to evade the innate immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / immunology*
  • Genome, Viral / genetics*
  • Humans
  • Interferons / immunology*
  • Phosphates
  • RNA Viruses / genetics*
  • RNA Viruses / pathogenicity
  • RNA, Viral / genetics
  • Virulence

Substances

  • Phosphates
  • RNA, Viral
  • Interferons
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases