RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates

Science. 2006 Nov 10;314(5801):997-1001. doi: 10.1126/science.1132998. Epub 2006 Oct 12.

Abstract

Double-stranded RNA (dsRNA) produced during viral replication is believed to be the critical trigger for activation of antiviral immunity mediated by the RNA helicase enzymes retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). We showed that influenza A virus infection does not generate dsRNA and that RIG-I is activated by viral genomic single-stranded RNA (ssRNA) bearing 5'-phosphates. This is blocked by the influenza protein nonstructured protein 1 (NS1), which is found in a complex with RIG-I in infected cells. These results identify RIG-I as a ssRNA sensor and potential target of viral immune evasion and suggest that its ability to sense 5'-phosphorylated RNA evolved in the innate immune system as a means of discriminating between self and nonself.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Cytoplasm / virology
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Dendritic Cells / virology
  • Encephalomyocarditis virus / genetics
  • Encephalomyocarditis virus / immunology
  • Encephalomyocarditis virus / metabolism
  • Genome, Viral
  • Humans
  • Immunity, Innate*
  • Influenza A virus / genetics*
  • Influenza A virus / immunology*
  • Influenza A virus / metabolism
  • Influenza A virus / physiology
  • Interferon-alpha / biosynthesis
  • Interferon-beta / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Phosphates / metabolism
  • Phosphorylation
  • RNA Caps / metabolism
  • RNA, Double-Stranded / metabolism
  • RNA, Viral / chemistry
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*
  • Receptors, Immunologic
  • Recombinant Fusion Proteins / metabolism
  • Transfection
  • Vesicular stomatitis Indiana virus / genetics
  • Vesicular stomatitis Indiana virus / immunology
  • Vesicular stomatitis Indiana virus / metabolism
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism
  • Virus Replication

Substances

  • INS1 protein, influenza virus
  • Interferon-alpha
  • Phosphates
  • RNA Caps
  • RNA, Double-Stranded
  • RNA, Viral
  • Receptors, Immunologic
  • Recombinant Fusion Proteins
  • Viral Nonstructural Proteins
  • Interferon-beta
  • RIGI protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases