Cited by 3,444Immune Response and Inflammationinterferon and immune responsesImmunotherapy and Immune Responses

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

Diebold, Sandra S., Kaisho, Tsuneyasu, Hemmi, Hiroaki, Akira, Shizuo, Reis e Sousa, Caetano·2004·Science

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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.

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Toll-Like Receptors
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Wkly. Epidemiol. Rec. No. 78 (2003), p. 39.
C. Reis e Sousa, Semin. Immunol.16, 24 (2004).
This work was funded by Cancer Research UK. We thank J. Skehel for providingstrain X31 for RNA isolation; M. Albert for wild-type PR8 flu; A. Grassauer and H. Unger for the ΔNS1 flu; A. Steinkasserer for pGEM4Z/GFP; G. Schiavo and G. Hammond for help with liposome preparation; and F. Batista I. Kerr J. Skehel R. Treisman and members of the Immunobiology Laboratory for advice and critical review of the manuscript.

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Authors: Diebold, S. S., Kaisho, T., Hemmi, H., Akira, S., & Reis e Sousa, C.
Affiliations: Cancer Research UK (GB)
Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.
ORCID: Diebold, Sandra S.
Kaisho, Tsuneyasu
Hemmi, Hiroaki
Akira, Shizuo
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2004-03-05
Volume: 303
Issue: 5663
Pages: 1529-1531
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1093616
OpenAlex: W1994391392
Cited by: 3,444
References: 24
Citations by year: 2026: 72 · 2025: 84 · 2024: 93 · 2023: 101 · 2022: 117 · 2021: 136 · 2020: 133 · 2019: 113 · 2018: 115 · 2017: 117 · 2016: 127 · 2015: 135 · 2014: 161 · 2013: 166 · 2012: 169
FWCI: 93.25
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Research Portal (King's College London) (submittedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: TLR7, single-stranded RNA, antiviral innate immunity, interferon-alpha, plasmacytoid dendritic cells, influenza virus, MyD88 signaling, RNA virus detection, inflammatory cytokines
MeSH terms: Animals, Antigens, Differentiation, Cells, Cultured, Dendritic Cells, Endocytosis, Immunity, Innate, Ligands, Membrane Glycoproteins, Mice, Inbred BALB C, Mice, Inbred C57BL, Influenza A virus, Poly U, Polyribonucleotides, Receptors, Cell Surface, Receptors, Immunologic, Endosomes, RNA, RNA, Viral, Signal Transduction, Cytokines, Genome, Viral, Interferon-alpha, Adaptor Proteins, Signal Transducing, Toll-Like Receptor 7, Mice, Myeloid Differentiation Factor 88

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

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