先天免疫是防止病毒感染的一個重要機(jī)制,，由宿主對PAMPS（與病原體相關(guān)的分子模式）的識別觸發(fā)?，F(xiàn)在，Saito等人識別出，丙肝病毒基因組的3′非轉(zhuǎn)錄區(qū)中的一個保留下來的多尿苷主題是可被RNA解旋酶RIG-I檢測到的相關(guān)PAMP,。以前的研究表明,，該解旋酶是在雙鏈RNA誘導(dǎo)的先天抗病毒反應(yīng)中發(fā)揮重要功能的一種蛋白。（生物谷Bioon.com）
生物谷推薦原始出處：
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: [email protected]).
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-/ 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.
