Comparative analysis of viral RNA signatures on different RIG-I-like receptors

Elife. 2016 Mar 24;5:e11275. doi: 10.7554/eLife.11275.

Abstract

The RIG-I-like receptors (RLRs) play a major role in sensing RNA virus infection to initiate and modulate antiviral immunity. They interact with particular viral RNAs, most of them being still unknown. To decipher the viral RNA signature on RLRs during viral infection, we tagged RLRs (RIG-I, MDA5, LGP2) and applied tagged protein affinity purification followed by next-generation sequencing (NGS) of associated RNA molecules. Two viruses with negative- and positive-sense RNA genome were used: measles (MV) and chikungunya (CHIKV). NGS analysis revealed that distinct regions of MV genome were specifically recognized by distinct RLRs: RIG-I recognized defective interfering genomes, whereas MDA5 and LGP2 specifically bound MV nucleoprotein-coding region. During CHIKV infection, RIG-I associated specifically to the 3' untranslated region of viral genome. This study provides the first comparative view of the viral RNA ligands for RIG-I, MDA5 and LGP2 in the presence of infection.

Keywords: PAMP; PRR; RIG-I-like receptors; human; immunology; infectious disease; innate immunity; microbiology; ribonucleoproteins; virus-host interactions.

MeSH terms

  • Cell Line
  • Chikungunya virus / immunology*
  • DEAD Box Protein 58 / metabolism*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Interferon-Induced Helicase, IFIH1 / isolation & purification
  • Interferon-Induced Helicase, IFIH1 / metabolism*
  • Measles virus / immunology*
  • RNA Helicases / isolation & purification
  • RNA Helicases / metabolism*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*
  • Receptors, Immunologic / isolation & purification
  • Receptors, Immunologic / metabolism*

Substances

  • RNA, Viral
  • Receptors, Immunologic
  • DHX58 protein, human
  • DDX58 protein, human
  • IFIH1 protein, human
  • DEAD Box Protein 58
  • Interferon-Induced Helicase, IFIH1
  • RNA Helicases

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.