Nature：丙肝病毒的识别
专题：Nature报道
先天免疫是防止病毒感染的一个重要机制，由宿主对PAMPS（与病原体相关的分子模式）的识别触发。现在，Saito等人识别出，丙肝病毒基因组的3′非转录区中的一个保留下来的多尿苷主题是可被RNA解旋酶RIG-I检测到的相关PAMP。以前的研究表明，该解旋酶是在双链RNA诱导的先天抗病毒反应中发挥重要功能的一种蛋白。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 454, 523-527 (24 July 2008) | doi:10.1038/nature07106
Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA
Takeshi Saito1, David M. Owen1,2, Fuguo Jiang3, Joseph Marcotrigiano3 & Michael Gale Jr.1
- Department of Immunology, University of Washington School of Medicine, Seattle, Washington 98195-7650, USA
- Department of Microbiology, UT Southwestern Medical Center, Dallas, Texas 75235-9048, USA
- Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, USA
Correspondence to: Michael Gale Jr.1 Correspondence and requests for materials should be addressed to M.G. (Email: mgale@u.washington.edu).
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-
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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 intermediate as the PAMP substrate of RIG-I, and show that this and similar homopolyuridine or homopolyriboadenine motifs present in the genomes of RNA viruses are the chief feature of RIG-I recognition and immune triggering in human and murine cells8. 5' terminal triphosphate on the PAMP RNA was necessary but not sufficient for RIG-I binding, which was primarily dependent on 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 immunotherapy approaches.
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