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Science 314 (5801): 997-1001

Copyright © 2006 by the American Association for the Advancement of Science

RIG-I-Mediated Antiviral Responses to Single-Stranded RNA Bearing 5'-Phosphates

Andreas Pichlmair,1 Oliver Schulz,1 Choon Ping Tan,1 Tanja I. Näslund,2 Peter Liljeström,2 Friedemann Weber,3 Caetano Reis e Sousa1*

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.

1 Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.
2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 17177, Sweden.
3 Department of Virology, University of Freiburg, Freiburg 79104, Germany.

* To whom correspondence should be addressed. E-mail: caetano{at}

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Characterization of Chicken Mda5 Activity: Regulation of IFN-{beta} in the Absence of RIG-I Functionality.
A. J. Karpala, C. Stewart, J. McKay, J. W. Lowenthal, and A. G. D. Bean (2011)
J. Immunol. 186, 5397-5405
   Abstract »    Full Text »    PDF »
Genomic RNAs of Borna disease virus are elongated on internal template motifs after realignment of the 3' termini.
A. Martin, N. Hoefs, J. Tadewaldt, P. Staeheli, and U. Schneider (2011)
PNAS 108, 7206-7211
   Abstract »    Full Text »    PDF »
Adenovirus Virus-Associated RNAs Induce Type I Interferon Expression through a RIG-I-Mediated Pathway.
T. Minamitani, D. Iwakiri, and K. Takada (2011)
J. Virol. 85, 4035-4040
   Abstract »    Full Text »    PDF »
ARF-like Protein 16 (ARL16) Inhibits RIG-I by Binding with Its C-terminal Domain in a GTP-dependent Manner.
Y.-K. Yang, H. Qu, D. Gao, W. Di, H.-W. Chen, X. Guo, Z.-H. Zhai, and D.-Y. Chen (2011)
J. Biol. Chem. 286, 10568-10580
   Abstract »    Full Text »    PDF »
Crystal structure of RIG-I C-terminal domain bound to blunt-ended double-strand RNA without 5' triphosphate.
C. Lu, C. T. Ranjith-Kumar, L. Hao, C. C. Kao, and P. Li (2011)
Nucleic Acids Res. 39, 1565-1575
   Abstract »    Full Text »    PDF »
Recognition of Cytoplasmic RNA Results in Cathepsin-Dependent Inflammasome Activation and Apoptosis in Human Macrophages.
J. Rintahaka, N. Lietzen, T. Ohman, T. A. Nyman, and S. Matikainen (2011)
J. Immunol. 186, 3085-3092
   Abstract »    Full Text »    PDF »
Short Double-stranded RNAs with an Overhanging 5' ppp-Nucleotide, as Found in Arenavirus Genomes, Act as RIG-I Decoys.
J.-B. Marq, S. Hausmann, N. Veillard, D. Kolakofsky, and D. Garcin (2011)
J. Biol. Chem. 286, 6108-6116
   Abstract »    Full Text »    PDF »
The C Proteins of Human Parainfluenza Virus Type 1 Limit Double-Stranded RNA Accumulation That Would Otherwise Trigger Activation of MDA5 and Protein Kinase R.
J. Boonyaratanakornkit, E. Bartlett, H. Schomacker, S. Surman, S. Akira, Y.-S. Bae, P. Collins, B. Murphy, and A. Schmidt (2011)
J. Virol. 85, 1495-1506
   Abstract »    Full Text »    PDF »
Interferon Antagonist NSs of La Crosse Virus Triggers a DNA Damage Response-like Degradation of Transcribing RNA Polymerase II.
P. Verbruggen, M. Ruf, G. Blakqori, A. K. Overby, M. Heidemann, D. Eick, and F. Weber (2011)
J. Biol. Chem. 286, 3681-3692
   Abstract »    Full Text »    PDF »

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