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Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNA
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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“However, several RNA structural features have been described as immunostimulatory due to interactions with various RNA sensors such as Toll-like receptors, RIG-I, and PKR.”
From Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals (2015) · cites this paper as [8]
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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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Metadata
- 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.
- Venue
- Science
- Published
- 2004-03-05
- Volume
- 303
- Issue
- 5663
- Pages
- 1529-1531
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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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