RIG-I-mediated antiviral responses to single-stranded RNA bearing 5’-phosphates
Abstract
Double-stranded RNA (dsRNA) produced during viral replication is believed to be the critical trigger for activation of antiviral immunity mediated by the RNA helicase enzymes retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). We showed that influenza A virus infection does not generate dsRNA and that RIG-I is activated by viral genomic single-stranded RNA (ssRNA) bearing 5'-phosphates. This is blocked by the influenza protein nonstructured protein 1 (NS1), which is found in a complex with RIG-I in infected cells. These results identify RIG-I as a ssRNA sensor and potential target of viral immune evasion and suggest that its ability to sense 5'-phosphorylated RNA evolved in the innate immune system as a means of discriminating between self and nonself.
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Several RNA structural features are immunostimulatory due to interactions with RNA sensors such as Toll-like receptors, RIG-I, and PKR.
“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 [12]
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- Authors
- Pichlmair, A., Schulz, O., Tan, C. P., Näslund, T. I., Liljeström, P., Weber, F., & Reis e Sousa, C.
- Affiliations
- University of Freiburg (DE)
- Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.
- Venue
- Science
- Published
- 2006-11-10
- Volume
- 314
- Issue
- 5801
- Pages
- 997-1001
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2009127910
- Cited by
- 2,210
- References
- 22
- Citations by year
- 2026: 40 · 2025: 55 · 2024: 64 · 2023: 55 · 2022: 89 · 2021: 94 · 2020: 116 · 2019: 95 · 2018: 101 · 2017: 102 · 2016: 100 · 2015: 111 · 2014: 137 · 2013: 148 · 2012: 127
- FWCI
- 59.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- RIG-I, MDA5, single-stranded RNA, influenza A virus, NS1 protein, antiviral innate immunity, RNA helicase, self/non-self discrimination, viral immune evasion, double-stranded RNA
- MeSH terms
- DEAD Box Protein 58, Animals, Cell Line, Cells, Cultured, Cytoplasm, Dendritic Cells, Encephalomyocarditis virus, Humans, Immunity, Innate, Mice, Inbred C57BL, Influenza A virus, Phosphates, Phosphorylation, Receptors, Immunologic, Recombinant Fusion Proteins, RNA Caps, RNA, Double-Stranded, RNA, Viral, Transfection, Vesicular stomatitis Indiana virus, Virus Replication, Genome, Viral, Interferon-alpha, Interferon-beta, Viral Nonstructural Proteins, Mice, DEAD-box RNA Helicases
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