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The structural basis for the distinction of viral RNA from abundantself RNA in the cytoplasm of virally infected cells is largelyunknown. We demonstrated that the 5'-triphosphate end of RNAgenerated by viral polymerases is responsible for retinoic acid–inducibleprotein I (RIG-I)–mediated detection of RNA molecules.Detection of 5'-triphosphate RNA is abrogated by capping ofthe 5'-triphosphate end or by nucleoside modification of RNA,both occurring during posttranscriptional RNA processing ineukaryotes. Genomic RNA prepared from a negative-strand RNAvirus and RNA prepared from virus-infected cells (but not fromnoninfected cells) triggered a potent interferon- response ina phosphatase-sensitive manner. 5'-triphosphate RNA directlybinds to RIG-I. Thus, uncapped 5'-triphosphate RNA (now termed3pRNA) present in viruses known to be recognized by RIG-I, butabsent in viruses known to be detected by MDA-5 such as thepicornaviruses, serves as the molecular signature for the detectionof 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}ukb.uni-bonn.de
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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. 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. 
