ABSTRACT Innate immune defences are essential for the control of virus infection and are triggered through host recognition of viral macromolecular motifs known as pathogen-associated

molecular patterns (PAMPs)1. Hepatitis C virus (HCV) is an RNA virus that replicates in the liver, and infects 200 million people worldwide2. Infection is regulated by hepatic immune

defences triggered by the cellular RIG-I helicase. RIG-I binds PAMP RNA and signals interferon regulatory factor 3 activation to induce the expression of interferon-α/β and

antiviral/interferon-stimulated genes (ISGs) that limit infection3,4,5,6,7,8,9,10. Here we identify the polyuridine motif of the HCV genome 3′ non-translated region and its replication

homopolymeric ribonucleotide composition, linear structure and length. The HCV PAMP RNA stimulated RIG-I-dependent signalling to induce a hepatic innate immune response _in vivo_, and

triggered interferon and ISG expression to suppress HCV infection _in vitro_. These results provide a conceptual advance by defining specific homopolymeric RNA motifs within the genome of

HCV and other RNA viruses as the PAMP substrate of RIG-I, and demonstrate immunogenic features of the PAMP–RIG-I interaction that could be used as an immune adjuvant for vaccine and

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innate immune response. _Nature_ 448, 501–505 (2007) Article  CAS  ADS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank T. Fujita for discussions, and S. Horner for manuscript

review. We thank T. Fujita, S. Lemon, G. Sen, C. Rice, T. Taniguchi, A. Miyawaki, S. Akira for reagents, R. Hirai for technical consultation, and J. Briley, S. Thomas and G. Martin for

technical assistance. This work was supported by funds from the State of Washington, National Institutes of Health grants R01AI060389, R01DA021353, U19AI40035 (Project 4) and the

Burroughs-Wellcome Fund, and by a gift from Mr. and Mrs. R. Batcheldor. AUTHOR CONTRIBUTIONS T.S. conducted RNA binding studies and RIG-I signalling analyses. T.S. and D.M.O. conducted _in

vivo_ studies. F.J. and J.M. developed the RIG-I protein-expression system, and produced, purified and tested recombinant RIG-I proteins. M.G. directed the research. All authors participated

in study design and manuscript preparation. T.S. wrote the manuscript. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Immunology, University of Washington School of Medicine,

Seattle, Washington 98195-7650, USA, Takeshi Saito, David M. Owen & Michael Gale Jr. * Department of Microbiology, UT Southwestern Medical Center, Dallas, Texas 75235-9048, USA, David M.

Owen * Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, USA, Fuguo Jiang & Joseph Marcotrigiano Authors * Takeshi Saito View author

publications You can also search for this author inPubMed Google Scholar * David M. Owen View author publications You can also search for this author inPubMed Google Scholar * Fuguo Jiang

View author publications You can also search for this author inPubMed Google Scholar * Joseph Marcotrigiano View author publications You can also search for this author inPubMed Google

Scholar * Michael Gale Jr. View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Michael Gale Jr.. SUPPLEMENTARY

INFORMATION SUPPLEMENTARY INFORMATION The file contains Supplementary Methods, Supplementary Tables S1-S2 and Supplementary Figures S1-S7 with legends and additional references. (PDF 1189

kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Saito, T., Owen, D., Jiang, F. _et al._ Innate immunity induced by composition-dependent RIG-I

recognition of hepatitis C virus RNA. _Nature_ 454, 523–527 (2008). https://doi.org/10.1038/nature07106 Download citation * Received: 13 February 2008 * Accepted: 23 May 2008 * Published: 01

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