Over the last half of century interferon (IFN), originally discovered as an antiviral protein, has developed from an inhibitor of viral replication to a major force in the antiviral response. Initially studied only by few virologists, IFN was generally considered as a poorly defined protein of limited importance. The development of molecular techniques lead to the identification of a family of IFN genes and has shown an unexpected complexity of type I IFN genes and their expression. Presently, some aspects of the of the pathogen mediated induction of IFN gene expression are understood at molecular level, while others are still at the stage of description. Both Toll like receptors and cytoplasmic RNA helicases were shown to recognize viral nucleic acids and the basis of a distinct recognition of viral nucleic acids from the cellular ones are emerging. Important insights on the virus recognition entity, leading to the expression of interferon and interferon induced genes, have been made in the recent year, which are challenging the accepted concept of the critical role of dsRNA in IFN induction. The availability of genetically modified mice that are lacking either essential components of the interferon inducing pathway, or interferon signaling pathway fully confirmed the original idea, made soon after its discovery, that interferon is the first cellular defense against viral infection.
Covers recent developments in a vital area of research
Reflections.- 1.1 Jean Linndemann: How to chase a red herring and come up with a Smallmouth Bass. - 1.2 J. Vilcek: Interferon research before BC (before cloning).- 1.3 S. Pestka: Purification and cloning of Interferon Alpha.- Interferons and their signaling pathways.- 2.1 P. Pitha and M. Kunzi: Type I Interferon: the ever unfolding story.- 2.2 G. Uze, G. Schreiber, J. Piehler and S. Pellegrini: The receptor of the type I interferon family.- 2.3 H. Young and J. Bream: IFN: Recent Advances I Understanding Regulation of Expression, Biological Functions and Clinical Application.- 2.4 A. van Boxel-Dezaire and G. Stark: Cell Type –Specific Signaling in response to Interferon gamma.- 2.5 J. Darnell: Interferon Research; Impact on understanding transcriptional control.- Recognition of pathogens, molecular mechanism of interferon beta induction.- 3.1 M. Severa and K. Fitzgerald: TLR-mediated activation of type I IFN during antiviral immine responses:fighting the battle to win the war.- 3.2 K. Onomoto, M. Yopeneyma and T. Fujita: Regulation of Antiviral Immune Response by RIG-I family of RNA helicases.- 3.3 M.Schlee, W.Barchets, V.Hornung and G.Hartmann: Beyond double stranded RNA-type I IFN induction by 3pRNA and other viral nucleic acids.- Interferon induced genes.- 4.1 G. Sen and S. Sarkar: The Interferon-Stimulated Genes: Targets of direct signaling by interferon, double –stranded RNA and viruses.- 4.2 A.Sadler and B. Williams: Structure and Function of the Protein Kinase R.- Virus defense.- 5.1 Y-M Loo and M. Gale: Viral Regulation and Evasion of the host response.- 5.2. O.Haller and F.Weber: Pathogenic Viruses: Smart Manipulators of the Interferon System.- Role of interferon in viral infection and autoimmunity.- 6.1 E. Zuniga, B. Hahm and M. Oldstone: Type I IFN during viralinfection: multiple triggers for a multifunctiona mediator.- 6.2 S. Crow: Type I FN in Systemic Lupus Erythematosus.-