Cited by 2,210interferon and immune responsesImmune Response and InflammationRNA regulation and disease

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RIG-I-mediated antiviral responses to single-stranded RNA bearing 5’-phosphates

Pichlmair, Andreas, Schulz, Oliver, Tan, Choon Ping, Näslund, Tanja I., Liljeström, Peter, Weber, Friedemann, Reis e Sousa, Caetano·2006·Science

DOI 10.1126/science.1132998

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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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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.
ORCID: Pichlmair, Andreas
Schulz, Oliver
Weber, Friedemann
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2006-11-10
Volume: 314
Issue: 5801
Pages: 997-1001
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1132998
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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RIG-I-mediated antiviral responses to single-stranded RNA bearing 5’-phosphates

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