certain chemokines correlate with good/poor outcome of HCV therapy

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-alpha/beta 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.

Following on the heels of World Hepatitis Day on 19 May 2008, this week’s issue of Eurosurveillance is a special issue on viral hepatitis, highlighting the various aspects and challenges related to hepatitis B and C. World Hepatitis Day was launched in 2007 to increase awareness and political commitment to tackling the significant problems viral hepatitis B and C pose to public health and to call for more control and prevention activities. In particular, chronic hepatitis B and C infections are a significant threat to public health, and are considered to be the leading causes of liver cancer worldwide. Hepatitis B and C occur with a very high burden of disease.