IFIT1 Is an Antiviral Protein That Recognizes 5'-triphosphate RNA

Nat Immunol. 2011 Jun 5;12(7):624-30. doi: 10.1038/ni.2048.

Abstract

Antiviral innate immunity relies on the recognition of microbial structures. One such structure is viral RNA that carries a triphosphate group on its 5' terminus (PPP-RNA). By an affinity proteomics approach with PPP-RNA as the 'bait', we found that the antiviral protein IFIT1 (interferon-induced protein with tetratricopeptide repeats 1) mediated binding of a larger protein complex containing other IFIT family members. IFIT1 bound PPP-RNA with nanomolar affinity and required the arginine at position 187 in a highly charged carboxy-terminal groove of the protein. In the absence of IFIT1, the growth and pathogenicity of viruses containing PPP-RNA was much greater. In contrast, IFIT proteins were dispensable for the clearance of pathogens that did not generate PPP-RNA. On the basis of this specificity and the great abundance of IFIT proteins after infection, we propose that the IFIT complex antagonizes viruses by sequestering specific viral nucleic acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / chemistry
  • Arginine / genetics
  • Arginine / immunology*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Female
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Viral / immunology*
  • RNA-Binding Proteins
  • Viruses / immunology*

Substances

  • Carrier Proteins
  • IFIT1 protein, human
  • Ifit1 protein, mouse
  • RNA, Viral
  • RNA-Binding Proteins
  • Arginine