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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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