For those inclined to read on immune system's self-control there is a recent review article on virus-host-immunity interactions, appearing in the SCIENCE STKE online site. Below I paste just the abstract of it. I should add that both HCV protease and immune system's self-control molecule LGP2 bind the same site on IPS1 to cut off signaling from a viral RNA detector RIG1. The fact that our immune system cannot distinguish HCV from self-control mechanism is an inherent "defect" in our immune system. The best, perhaps only way to repair the "defect" for now is to take a good protease inhibitor like TVR only after infection. No vaccines can be developed because HCV sabotages vaccine-induced immunity also.
Sci. STKE, 1 May 2007Vol. 2007, Issue 384, p. pe20[DOI: 10.1126/stke.3842007pe20] PERSPECTIVES Regulation of Interferon Production by RIG-I and LGP2: A Lesson in Self-Control Damien Vitour and Eliane F. Meurs* Hepacivirus Unit, Pasteur Institute, Paris Cedex 15, France Abstract: The cytoplasmic CARD-containing DExD/H box RNA helicases RIG-I and MDA5 act as sensors of viral infections through recognition of viral double-stranded (ds) RNAs. They both associate with the mitochondrial adaptor IPS-1 (also referred to as MAVS, VISA, and CARDIF) through homotypic CARD-CARD interactions. IPS-1, in turn, triggers signaling pathways, including activation of the protein kinases TBK1 and IKK , responsible for the phosphorylation of IRF3, a key transcription factor involved in interferon (IFN) synthesis, one essential element of the innate immune response. RIG-I remains in an autoinhibited state in the absence of dsRNA, through an internal repressor domain (RD) that binds within both its CARD and its RNA helicase domains and therefore acts in cis to control its multimerization and interaction with IPS-1. Ectopic expression of the RD prevents signaling and increases cell permissiveness to viruses, including hepatitis C virus. LGP2, which is another DExD/H RNA helicase of the RIG-I and MDA5 family and which is devoid of CARD domain, negatively controls IFN induction at different levels: by sequestering dsRNA, by blocking RIG-I�s multimerization in trans through a domain analogous to the RIG-I RD, and by competing with the protein kinase IKK for a common interaction site on IPS-1. The ability of RIG-I and LGP2 to exert such a feedback control at the earliest steps of IFN synthesis allows the cells to exert a tight regulation of the induction of the innate immune response. *Corresponding author: Address, Unit Hepacivirus, Department Virology, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France; telephone, (33) 1 45 68 87 77; fax, (33) 1 40 61 30 12; e-mail, firstname.lastname@example.org Citation: D. Vitour, E. F. Meurs, Regulation of Interferon Production by RIG-I and LGP2: A Lesson in Self-Control. Sci. STKE 2007, pe20 (2007).