Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA

Science. 2004 Mar 5;303(5663):1529-31. doi: 10.1126/science.1093616. Epub 2004 Feb 19.

Abstract

Interferons (IFNs) are critical for protection from viral infection, but the pathways linking virus recognition to IFN induction remain poorly understood. Plasmacytoid dendritic cells produce vast amounts of IFN-alpha in response to the wild-type influenza virus. Here, we show that this requires endosomal recognition of influenza genomic RNA and signaling by means of Toll-like receptor 7 (TLR7) and MyD88. Single-stranded RNA (ssRNA) molecules of nonviral origin also induce TLR7-dependent production of inflammatory cytokines. These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, Differentiation / metabolism
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Dendritic Cells / immunology*
  • Endocytosis
  • Endosomes / immunology
  • Endosomes / virology
  • Genome, Viral
  • Immunity, Innate*
  • Influenza A virus / genetics
  • Influenza A virus / immunology*
  • Interferon-alpha / biosynthesis
  • Ligands
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Myeloid Differentiation Factor 88
  • Poly U / immunology
  • Polyribonucleotides / immunology
  • RNA / immunology*
  • RNA, Viral / immunology*
  • Receptors, Cell Surface / metabolism*
  • Receptors, Immunologic / metabolism
  • Signal Transduction
  • Toll-Like Receptor 7

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Cytokines
  • Interferon-alpha
  • Ligands
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Polyribonucleotides
  • RNA, Viral
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Poly U
  • RNA