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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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Highly Pathogenic Avian Influenza H5N1 Viruses Elicit an Attenuated Type I Interferon Response in Polarized Human Bronchial Epithelial Cells.
H. Zeng, C. Goldsmith, P. Thawatsupha, M. Chittaganpitch, S. Waicharoen, S. Zaki, T. M. Tumpey, and J. M. Katz (2007)
J. Virol.
81, 12439-12449
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Regulation of IRF-3-dependent Innate Immunity by the Papain-like Protease Domain of the Severe Acute Respiratory Syndrome Coronavirus.
S. G. Devaraj, N. Wang, Z. Chen, Z. Chen, M. Tseng, N. Barretto, R. Lin, C. J. Peters, C.-T. K. Tseng, S. C. Baker, et al. (2007)
J. Biol. Chem.
282, 32208-32221
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The Npro product of classical swine fever virus and bovine viral diarrhea virus uses a conserved mechanism to target interferon regulatory factor-3.
J. Seago, L. Hilton, E. Reid, V. Doceul, J. Jeyatheesan, K. Moganeradj, J. McCauley, B. Charleston, and S. Goodbourn (2007)
J. Gen. Virol.
88, 3002-3006
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Differential Type I IFN-Inducing Abilities of Wild-Type versus Vaccine Strains of Measles Virus.
M. Shingai, T. Ebihara, N. A. Begum, A. Kato, T. Honma, K. Matsumoto, H. Saito, H. Ogura, M. Matsumoto, and T. Seya (2007)
J. Immunol.
179, 6123-6133
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Vesicular Stomatitis Virus mRNA Capping Machinery Requires Specific cis-Acting Signals in the RNA.
J. T. Wang, L. E. McElvain, and S. P. J. Whelan (2007)
J. Virol.
81, 11499-11506
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Role for the Phosphoprotein P Subunit of the Paramyxovirus Polymerase in Limiting Induction of Host Cell Antiviral Responses.
Differential Role of TLR- and RLR-Signaling in the Immune Responses to Influenza A Virus Infection and Vaccination.
S. Koyama, K. J. Ishii, H. Kumar, T. Tanimoto, C. Coban, S. Uematsu, T. Kawai, and S. Akira (2007)
J. Immunol.
179, 4711-4720
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IFN Regulatory Factor Family Members Differentially Regulate the Expression of Type III IFN (IFN-{lambda}) Genes.
P. I. Osterlund, T. E. Pietila, V. Veckman, S. V. Kotenko, and I. Julkunen (2007)
J. Immunol.
179, 3434-3442
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Persistent and Stable Gene Expression by a Cytoplasmic RNA Replicon Based on a Noncytopathic Variant Sendai Virus.
K. Nishimura, H. Segawa, T. Goto, M. Morishita, A. Masago, H. Takahashi, Y. Ohmiya, T. Sakaguchi, M. Asada, T. Imamura, et al. (2007)
J. Biol. Chem.
282, 27383-27391
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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. 
