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Science 314 (5801): 994-997

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

5'-Triphosphate RNA Is the Ligand for RIG-I

Veit Hornung,1 Jana Ellegast,1 Sarah Kim,1 Krzysztof Brzózka,3 Andreas Jung,2 Hiroki Kato,2 Hendrik Poeck,1 Shizuo Akira,2 Karl-Klaus Conzelmann,3 Martin Schlee,4 Stefan Endres,1 Gunther Hartmann4*

Abstract: The structural basis for the distinction of viral RNA from abundant self RNA in the cytoplasm of virally infected cells is largely unknown. We demonstrated that the 5'-triphosphate end of RNA generated by viral polymerases is responsible for retinoic acid–inducible protein I (RIG-I)–mediated detection of RNA molecules. Detection of 5'-triphosphate RNA is abrogated by capping of the 5'-triphosphate end or by nucleoside modification of RNA, both occurring during posttranscriptional RNA processing in eukaryotes. Genomic RNA prepared from a negative-strand RNA virus and RNA prepared from virus-infected cells (but not from noninfected cells) triggered a potent interferon-{alpha} response in a phosphatase-sensitive manner. 5'-triphosphate RNA directly binds to RIG-I. Thus, uncapped 5'-triphosphate RNA (now termed 3pRNA) present in viruses known to be recognized by RIG-I, but absent in viruses known to be detected by MDA-5 such as the picornaviruses, serves as the molecular signature for the detection of viral infection by RIG-I.

1 Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.
2 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita 565–0871, Osaka, Japan.
3 Department of Virology, Max von Pettenkofer Institute and Gene Center, University of Munich, 81377 Munich, Germany.
4 Division of Clinical Pharmacology, University Hospital, University of Bonn, 53105 Bonn, Germany.

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

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   Abstract »    Full Text »    PDF »
TLR7/9 versus TLR3/MDA5 signaling during virus infections and diabetes.
M. Swiecki, S. A. McCartney, Y. Wang, and M. Colonna (2011)
J. Leukoc. Biol. 90, 691-701
   Abstract »    Full Text »    PDF »
Induction of Innate Immune Responses by SIV In Vivo and In Vitro: Differential Expression and Function of RIG-I and MDA5.
J. G. Co, K. W. Witwer, L. Gama, M. C. Zink, and J. E. Clements (2011)
The Journal of Infectious Disease 204, 1104-1114
   Abstract »    Full Text »    PDF »
DDX60, a DEXD/H Box Helicase, Is a Novel Antiviral Factor Promoting RIG-I-Like Receptor-Mediated Signaling.
M. Miyashita, H. Oshiumi, M. Matsumoto, and T. Seya (2011)
Mol. Cell. Biol. 31, 3802-3819
   Abstract »    Full Text »    PDF »
Interplay between Innate Immunity and Negative-Strand RNA Viruses: towards a Rational Model.
D. Gerlier and D. S. Lyles (2011)
Microbiol. Mol. Biol. Rev. 75, 468-490
   Abstract »    Full Text »    PDF »
Alleles A and B of non-structural protein 1 of avian influenza A viruses differentially inhibit beta interferon production in human and mink lung cells.
M. Munir, S. Zohari, G. Metreveli, C. Baule, S. Belak, and M. Berg (2011)
J. Gen. Virol. 92, 2111-2121
   Abstract »    Full Text »    PDF »
Innate Immune Responses in Human Monocyte-Derived Dendritic Cells Are Highly Dependent on the Size and the 5' Phosphorylation of RNA Molecules.
M. Jiang, P. Osterlund, L. P. Sarin, M. M. Poranen, D. H. Bamford, D. Guo, and I. Julkunen (2011)
J. Immunol. 187, 1713-1721
   Abstract »    Full Text »    PDF »
Molecular Mechanism of Signal Perception and Integration by the Innate Immune Sensor Retinoic Acid-inducible Gene-I (RIG-I).
M. Binder, F. Eberle, S. Seitz, N. Mucke, C. M. Huber, N. Kiani, L. Kaderali, V. Lohmann, A. Dalpke, and R. Bartenschlager (2011)
J. Biol. Chem. 286, 27278-27287
   Abstract »    Full Text »    PDF »
Human T Cell Leukemia Virus Type 1 Tax Inhibits Innate Antiviral Signaling via NF-{kappa}B-Dependent Induction of SOCS1.
S. Charoenthongtrakul, Q. Zhou, N. Shembade, N. S. Harhaj, and E. W. Harhaj (2011)
J. Virol. 85, 6955-6962
   Abstract »    Full Text »    PDF »
Ambivalent Role of the Innate Immune Response in Rabies Virus Pathogenesis.
D. Chopy, J. Pothlichet, M. Lafage, F. Megret, L. Fiette, M. Si-Tahar, and M. Lafon (2011)
J. Virol. 85, 6657-6668
   Abstract »    Full Text »    PDF »
RNA Structural Domains in Noncoding Regions of the Foot-and-Mouth Disease Virus Genome Trigger Innate Immunity in Porcine Cells and Mice.
M. Rodriguez-Pulido, B. Borrego, F. Sobrino, and M. Saiz (2011)
J. Virol. 85, 6492-6501
   Abstract »    Full Text »    PDF »
Activation of Endothelial Toll-Like Receptor 3 Impairs Endothelial Function.
S. Zimmer, M. Steinmetz, T. Asdonk, I. Motz, C. Coch, E. Hartmann, W. Barchet, S. Wassmann, G. Hartmann, and G. Nickenig (2011)
Circ. Res. 108, 1358-1366
   Abstract »    Full Text »    PDF »

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