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

• Veit Hornung

  Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.

• Jana Ellegast

  Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.

• Sarah Kim

  Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.

• Krzysztof Brzózka

  Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.

• Andreas Jung

  Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.

• Hiroki Kato

  Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.

• Hendrik Poeck

  Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.

• Shizuo Akira

  Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.

• Karl-Klaus Conzelmann

  Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.

• Martin Schlee

  Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.

• Stefan Endres

  Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.

• Gunther Hartmann

  Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany.

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-α 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.

Journal

• Science

  Science 314 (5801), 994-997, 2006-11-10

  American Association for the Advancement of Science (AAAS)

Keywords

• Multidisciplinary

Details

• CRID: 1364233269629339776
• NII Article ID: 80018776801
• DOI: 10.1126/science.1132505
• ISSN: 10959203
• ISSN: 00368075
• ISSN: http://id.crossref.org/issn/00368075
• Web Site: https://www.science.org/doi/pdf/10.1126/science.1132505
• Data Source:
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  • CiNii Articles
  • KAKEN