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Annales de Biologie Clinique

Anti-viral proteins : from interferon alpha to its receptor Volume 57, numéro 3, Mai - Juin 1999

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  • Author(s): V. Chieux, D. Hober, W. Chehadeh, P. Wattré , Laboratoire de virologie, Institut Gernez-Rieux, Centre hospitalier et universitaire, Lille
  • Key words: Type I interferons – Interferon alpha sub-types – Type I interferons receptor – Transduction – Antiviral proteins.
  • Page(s) : 283-90
  • Published in: 1999

The immune response against viral pathogens include specific and non specific mechanisms. Cytokines are peptides which can play a role in the non specific immunity. Type I interferons (IFNalpha/beta) are the most effective antiviral cytokines. Interferons alpha are represented by a large familly of structurally related genes while the IFNbeta is encoded by a single gene. Type I interferon genes are located on the chromosome 9, and are segregated in a “modern” and an “ancestral” group with distinctive effects onto the cells. Type I interferons consist of 5 alpha helices, 4 of which are closely held together. Type I interferons receptor is a member of the class II cytokine receptor familly. It is a heterodimer composed of polypeptidic chains naimed IFNAR-1 and IFNAR-2. The type I interferons inducers are viruses, inactivated viruses and certain synthetic molecules. The molecular mechanisms of the induction of IFNbeta have been extensively described whereas the factors that play a role in the regulation of IFNalpha are not so well characterized. Two regulating domains located on the IFNbeta gene promotor are involved. The activation of these regulating domains leads to adverse effects by interacting with two intracellular factors (IRF1 and IRF2). IRF1 enhances the synthesis of IFNbeta but other pathways may be involved as well. The different IFNalpha sub-types have not only synergistic but also antagonistic effects. The synthesis of the different subtypes depends on cell lines and IFNalpha inducers. The N terminal part of IFNalpha is a major determinant in the diversity of the biological effects of IFNalpha sub-types which probably involve changes of the conformation of the type I receptor resulting from interactions between the receptor and its ligand. The type I interferons confer resistance to viruses, especially by enhancing the synthesis of intracellular antiviral proteins.