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Submitted on July 14, 2006
Accepted on September 18, 2006
5'-Triphosphate RNA Is the Ligand for RIG-I
Veit Hornung 1, Jana Ellegast 1, Sarah Kim 1, Krzysztof Brzózka 2, Andreas Jung 3, Hiroki Kato 3, Hendrik Poeck 1, Shizuo Akira 3, Karl-Klaus Conzelmann 2, Martin Schlee 4, Stefan Endres 1, Gunther Hartmann 4*
1 Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany. 2 Department of Virology, Max von Pettenkofer Institute and Gene Center, University of Munich, 81377 Munich, Germany. 3 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Osaka, Japan. 4 Division of Clinical Pharmacology, University Hospital, University of Bonn, 53105 Bonn, Germany.
* To whom correspondence should be addressed.
Gunther Hartmann , E-mail: gunther.hartmann{at}ukb.uni-bonn.de
The structural basis for the distinction of viral RNA from abundantself-RNA in the cytoplasm of virally infected cells is largelyunknown. Here we demonstrate that the 5'-triphosphate end ofRNA generated by viral polymerases is responsible for RIG-I-mediateddetection of RNA molecules. Detection of 5'-triphosphate RNAis abrogated by capping of the 5'-triphosphate end or by nucleosidemodification of RNA, both occurring during posttranscriptionalRNA processing in eukaryotes. Genomic RNA prepared from a negativestrand RNA virus and RNA prepared from virus-infected cells,but not RNA from non-infected cells triggered a potent IFN-response in a phosphatase sensitive manner. 5'-triphosphateRNA directly binds to RIG-I. In conclusion, uncapped 5'-triphosphateRNA present in viruses known to be recognized via RIG-I, butabsent in viruses known to be detected via MDA-5 such as Picornaviruses,serves as the molecular signature for the detection of viralinfection by RIG-I.
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Phagocytosis of Picornavirus-Infected Cells Induces an RNA-Dependent Antiviral State in Human Dendritic Cells.
M. Kramer, B. M. Schulte, L. W. J. Toonen, P. M. Barral, P. B. Fisher, K. H. W. Lanke, J. M. D. Galama, F. J. M. van Kuppeveld, and G. J. Adema (2008)
J. Virol.
82, 2930-2937
|Abstract »|Full Text »|PDF »
A Repetitive Region of Gammaherpesvirus Genomic DNA Is a Ligand for Induction of Type I Interferon.
D. J. Sanchez, D. Miranda Jr., V. Arumugaswami, S. Hwang, A. E. Singer, A. Senaati, A. Shahangian, M. J. Song, R. Sun, and G. Cheng (2008)
J. Virol.
82, 2208-2217
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Late Onset of Ccl2 Blockade with the Spiegelmer mNOX-E36-3'PEG Prevents Glomerulosclerosis and Improves Glomerular Filtration Rate in db/db Mice.
V. Ninichuk, S. Clauss, O. Kulkarni, H. Schmid, S. Segerer, E. Radomska, D. Eulberg, K. Buchner, N. Selve, S. Klussmann, et al. (2008)
Am. J. Pathol.
172, 628-637
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Cutting Edge: Innate Immune Response Triggered by Influenza A Virus Is Negatively Regulated by SOCS1 and SOCS3 through a RIG-I/IFNAR1-Dependent Pathway.
J. Pothlichet, M. Chignard, and M. Si-Tahar (2008)
J. Immunol.
180, 2034-2038
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Short-hairpin RNAs synthesized by T7 phage polymerase do not induce interferon.
T. Gondai, K. Yamaguchi, N. Miyano-Kurosaki, Y. Habu, and H. Takaku (2008)
Nucleic Acids Res.
36, e18
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Negative Feedback Regulation of RIG-I-Mediated Antiviral Signaling by Interferon-Induced ISG15 Conjugation.
M.-J. Kim, S.-Y. Hwang, T. Imaizumi, and J.-Y. Yoo (2008)
J. Virol.
82, 1474-1483
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Cytosolic Antiviral RNA Recognition Pathway Activates Caspases 1 and 3.
J. Rintahaka, D. Wiik, P. E. Kovanen, H. Alenius, and S. Matikainen (2008)
J. Immunol.
180, 1749-1757
|Abstract »|Full Text »|PDF »
response in a phosphatase sensitive manner. 5'-triphosphate RNA directly binds to RIG-I. In conclusion, uncapped 5'-triphosphate RNA present in viruses known to be recognized via RIG-I, but absent in viruses known to be detected via MDA-5 such as Picornaviruses, serves as the molecular signature for the detection of viral infection by RIG-I.
