5'-Triphosphate-RNA-independent activation of RIG-I via RNA aptamer with enhanced antiviral activity

Nucleic Acids Res. 2012 Mar;40(6):2724-33. doi: 10.1093/nar/gkr1098. Epub 2011 Nov 29.

Abstract

RIG-I is a cytosolic receptor for non-self RNA that mediates immune responses against viral infections through IFNα/β production. In an attempt to identify novel tools that modulate IFNα/β production, we used SELEX technology to screen RNA aptamers that specifically target RIG-I protein. Most of the selected RIG-I aptamers contained polyU motifs in the second half regions that played critical roles in the activation of RIG-I-mediated IFNβ production. Unlike other known ligands, RIG-I aptamer bound and activated RIG-I in a 5'-triphosphate-independent manner. The helicase and RD domain of RIG-I were used for aptamer binding, but intact RIG-I protein was required to exert aptamer-mediated signaling activation. Furthermore, replication of NDV, VSV and influenza virus in infected host cells was efficiently blocked by pre- or post-treatment with RIG-I aptamer. Based on these data, we propose that RIG-I aptamer has strong potential to be an antiviral agent that specifically boosts the RIG-I-dependent signaling cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / pharmacology*
  • Base Sequence
  • Cell Line
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / metabolism*
  • Humans
  • Interferon-beta / biosynthesis
  • Molecular Sequence Data
  • Poly U / chemistry
  • Polyphosphates / chemistry
  • RNA / chemistry
  • Receptors, Immunologic
  • SELEX Aptamer Technique
  • Signal Transduction / drug effects
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Aptamers, Nucleotide
  • Polyphosphates
  • Receptors, Immunologic
  • Poly U
  • RNA
  • Interferon-beta
  • RIGI protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • triphosphoric acid