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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- This work was funded by Cancer Research UK. We thank I. Kerr for SFV and EMCV T. Muster for ΔNS1 J. Skehel for purified influenza S. Diebold for flu vRNA isolation and GFP RNA synthesis A. Bergthaler for VSV vRNA J. Yewdell for the antibody to NS1 C. Basler for FLAG–RIG-I and A. Garcia-Sastre for NS1 constructs. We are grateful to members of the Immunobiology Laboratory for support.
Dates
Type | When |
---|---|
Created | 18 years, 10 months ago (Oct. 13, 2006, 6:40 a.m.) |
Deposited | 1 year, 7 months ago (Jan. 10, 2024, 4:28 a.m.) |
Indexed | 1 hour, 56 minutes ago (Aug. 24, 2025, 4:50 a.m.) |
Issued | 18 years, 9 months ago (Nov. 10, 2006) |
Published | 18 years, 9 months ago (Nov. 10, 2006) |
Published Print | 18 years, 9 months ago (Nov. 10, 2006) |
@article{Pichlmair_2006, title={RIG-I-Mediated Antiviral Responses to Single-Stranded RNA Bearing 5’-Phosphates}, volume={314}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1132998}, DOI={10.1126/science.1132998}, number={5801}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Pichlmair, Andreas and Schulz, Oliver and Tan, Choon Ping and Näslund, Tanja I. and Liljeström, Peter and Weber, Friedemann and Reis e Sousa, Caetano}, year={2006}, month=nov, pages={997–1001} }