Veit Hornung1,2,3,4, Jana M. Ellegast1,2,3,4, Sarah Kim-Hellmuth1,2,3,4, Krzysztof Brzózka1,2,4, Andreas Jung1,2,3,4, Hiroki Kato1,2,3,4, Hendrik Poeck1,2,3,4, Shizuo Akira1,2,3,4, Karl‐Klaus Conzelmann1,2,4, Martin Schlee1,2,3,4, Stefan Endres1,2,3,4, Gunther Hartmann1,2,3,4
1Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita 565–0871, Osaka, Japan.
2Department of Virology, Max von Pettenkofer Institute and Gene Center, University of Munich, 81377 Munich, Germany.
3Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, 80336 Munich, Germany
4Division of Clinical Pharmacology, University Hospital, University of Bonn, 53105 Bonn, Germany.
Tóm tắt
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.
