Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA

Takeshi Saito et al., Nature 454:523-527. (2008)

Speaker: 魏麗勳                                                          Time:13:00-14:00, Sep. 24, 2008

Commentator: 楊孔嘉 老師                                       Room:601

   Innate immunity senses virus infection by using host pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs) of the viral products¹. For hepatitis C virus (HCV) infection in liver, a PRR called RIG-I helicase plays an important role in detecting virus RNA, activating signal pathways for type I interferon (IFN), inducing expression of IFN-stimulated genes (ISGs), and exerting antiviral effects². However, the critical region of HCV RNA acting as the PAMP substrate of RIG-I is still uncertain. In this paper, the authors identified the 5’triphosphate-containing polyuridine (PU/UC) of HCV 3’ non-translated region and its replication intermediates as the PAMP substrates, revealing several features for composition-dependent RIG-I recognition. The 5’ terminal triphosphate (5’ppp) of PU/UC which releases RIG-I autorepressionwas necessary but not sufficient for RIG-I binding to its substrate. The authors further defined that 50 or more nucleotides of poly-U or poly-A RNAs are required for activating IFN-b responses. In a mouse model, PU/UC induced hepatic IFN-b and ISGs, and elevated serum IFN-b, in a RIG-I-dependent manner. In addition to the direct response, the paracrine IFN produced from PU/UC-transfected cells indirectly protected cells from HCV infection and replication. Moreover, IFN-b response can also be activated by PU/UC-like RNA motifs of other viruses such as rabies virus, Ebola virus and measles virus, indicating that PU/UC may be a general PAMP for RIG-I recognition and antiviral innate immunity. Therefore, PU/UC is a potentially useful adjuvant for vaccine development.

Reference

1.      Principles of intracellular viral recognition. Current Opinion in Immunology, 19:17–23.(2007)

2.      Evasion of intracellular host defence by hepatitis C virus. Nature, 436: 939-945.(2005)