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Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. May 7, 2007; 13(17): 2446-2454
Published online May 7, 2007. doi: 10.3748/wjg.v13.i17.2446
The interferon inducing pathways and the hepatitis C virus
Eliane F Meurs, Adrien Breiman
Eliane F Meurs, Pasteur Institute, Hepacivirus Unit, F-75015 Paris cedex, France
Adrien Breiman, Imperial College, Faculty of Medicine, Department of Virology, London W2 1PG, United Kingdom
Author contributions: All authors contributed equally to the work.
Supported by grants from the Agence Nationale pour la Recherche contre le SIDA
Correspondence to: Eliane F Meurs, Hepacivirus Unit, Department of Virology, Pasteur Institute, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.
Telephone: +33-1-45688777 Fax: +33-1-40613012
Received: December 23, 2006
Revised: December 28, 2006
Accepted: March 21, 2007
Published online: May 7, 2007

The innate immune response is triggered by a variety of pathogens, including viruses, and requires rapid induction of type I interferons (IFN), such as IFNβ and IFNα. IFN induction occurs when specific pathogen motifs bind to specific cellular receptors. In non-professional immune, virally-infected cells, IFN induction is essentially initiated after the binding of dsRNA structures to TLR3 receptors or to intracytosolic RNA helicases, such as RIG-I /MDA5. This leads to the recruitment of specific adaptors, such as TRIF for TLR3 and the mitochondrial-associated IPS-1/VISA/MAVS/CARDIF adapter protein for the RNA helicases, and the ultimate recruitment of kinases, such as MAPKs, the canonical IKK complex and the TBK1/IKKε kinases, which activate the transcription factors ATF-2/c-jun, NF-κB and IRF3, respectively. The coordinated action of these transcription factors leads to induction of IFN and of pro-inflammatory cytokines and to the establishment of the innate immune response. HCV can cleave both the adapters TRIF and IPS-1/VISA/MAVS/CARDIF through the action of its NS3/4A protease. This provokes abrogation of the induction of the IFN and cytokine pathways and favours viral propagation and presumably HCV chronic infection.

Keywords: Toll-like receptor, RNA helicase, Mitochondrial adapter Cardif, TBK1/IKKepsilon, Interferon induction, HCV NS3A protease