Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNA

• DOI: 10.1126/science.1093616
• Publication Date: 2004-02-24T01:52:29Z
• Authors: Hiroaki Hemmi; Shizuo Akira; Caetano Reis e Sousa; Tsuneyasu Kaisho; Sandra S. Diebold
• Keywords: Poly U; Mice, Inbred BALB C; Membrane Glycoproteins; Interferon-alpha; Dendritic Cells; Endosomes; Genome, Viral; Ligands; Antigens, Differentiation; Endocytosis; Immunity, Innate; 03 medical and health sciences; Influenza A virus; Myeloid Differentiation Factor 88; Cytokines; Cells, Cultured; Adaptor Proteins, Signal Transducing; Polyribonucleotides

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-α 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.