Interferon inducer

Abstract: Interferons have been shown to be potential anti-cancer agents and to inhibit tumor cell growth in culture. The in vivo mechanism of the anti-proliferative effect may be direct or indirect through the immune system; however, in vitro a primary mechanism of cytotoxicity is through the depletion of tryptophan. In particular, interferon-gamma (IFN-gamma) induces an enzyme of tryptophan catabolism, indoleamine 2,3-dioxygenase (IDO), which is responsible for conversion of tryptophan and other indole derivatives to kynurenine. The inhibitory effect of interferon on many intracellular parasites such as Toxoplasma gondii and Chlamydia trachomatis is by the same mechanism. Elevated kynurenine levels have been found in humans in a number of diseases and after interferon treatment, and the enzyme is induced in rodents after administration of interferon inducers, or influenza virus. IDO induction also occurs in vivo during rejection of allogeneic tumors, indicating a possible role for this enzyme in the tumor rejection process. The gene for IDO has been cloned and shown to be differentially regulated by IFN-alpha and IFN-gamma. IDO induction has been correlated with induction of GTP-cyclohydrolase, the key enzyme in pteridine biosynthesis. A direct role for IDO in pteridine synthesis has not been shown, and this parallel induction may reflect coordinate regulation of genes induced by IFN-gamma. A possible role for IDO in O2-radical scavenging and in inflammation is discussed.

Abstract: Over the past few years, several groups have identified new genes that are transcriptionally induced downstream of type I interferon (IFN) signalling and that inhibit infection by individual or multiple families of viruses. Among these IFN-stimulated genes with antiviral activity are two genetically and functionally distinct families--the IFN-induced protein with tetratricopeptide repeats (IFIT) family and the IFN-induced transmembrane protein (IFITM) family. This Review focuses on recent advances in identifying the unique mechanisms of action of IFIT and IFITM proteins, which explain their broad-spectrum activity against the replication, spread and pathogenesis of a range of human viruses.

Abstract: Publisher Summary Interferons (IFNs) are proteins or glycoproteins that are able to exert antiviral activity through their effects on the intracellular events of the viral cycle and were first defined in 1957. They belong to the family of biological response modifiers and are constituents of the body's defense system. IFNs can be induced in an organism by virus infection, a variety of nonviral inducers, mitogens, antigens, and tumor cells. As IFNs are produced under such varied circumstances, the exact role played by these molecules in connection with various disease states must be deciphered. Recombinant DNA technology has also had enormous impact on IFN research. The chapter discusses the three classes (α, β, and γ) of IFNs and explains the methods of production and purification of IFNs, interferon induction, and the production control and genetics of IFN system. The biochemical properties and structures of the various human IFNs, the IFN preparations used for clinical trials, and the genetics of IFN system are also discussed.