The interferon inducing pathways and the hepatitis C virus.
The innate immune response is triggered by a variety of pathogens, including viruses, and requires rapid induction of type I interferons (IFN), such as IFNbeta and IFNalpha. 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/IKKepsilon kinases, which activate the transcription factors ATF-2/c-jun, NF-kappaB 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.
Meurs
Eliane F
EF
Hepacivirus Unit, Department of Virology, Pasteur Institute, 28 rue du Dr Roux, 75724 Paris Cedex 15, France. emeurs@pasteur.fr
Breiman
Adrien
A
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020365:RNA Helicases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D051193:Toll-Like Receptors; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; D020365:RNA Helicases