Interferons action

The ability of interferons (especially type I interferons) to induce an antiviral state is unlikely to be solely dependent upon the enzymatic mechanisms discussed above. Furthermore the 2 -5 A synthetase and eIF-2a kinase systems may play important roles in mediating additional interferon actions. The ability of such systems to stall protein synthesis in cells may play a role in interferon-induced alterations of cellular differentiation or cell cycle progression. They may also be involved in mediating interferon-induced anti-proliferative effects on various transformed cells. 

Teaman, D.W, Mechanisms of interferon action. Prog Mol SnbceU Biol, 1998. 20 101-42. 

The possibility that interferons can be used as pharmacologic agents has aroused a great deal of interest. Recombinant DNA techniques and cell tissue cultures have been used to produce sufficient quantities of interferons for clinical drug trials. The rationale is that exogenously administered interferons will produce antiviral and other beneficial effects in healthy cells in a manner similar to their endogenously produced counterparts. Some of the pertinent aspects of interferon action and clinical applications are presented below. 

Experiments using TSH or cholera toxin as probes of the mechanism of interferon action also indicate the following (i) The initial binding of... 

Other routes of administration have been evaluated, such as inhalation, intrale-sional, intranasal, intraperitoneal, intraventricular, and intraocular rates, in clinical studies. For the most part, these alternative routes were attempts to improve the delivery of interferon to sites not easily accessible via the systemic circulation. These dosing strategies have provided adequate concentrations of interferon in cerebrospinal fluid, lymph, nasal mucosa, and peritoneal fluid, but have not led to clinical success, undoubtedly reflecting the lack of understanding of the inherent mechanism of interferon action [164]. 

Bischoff JR, Samuel CE (1985) Mechanism of interferon action. The interferon-induced phosphoprotein PI possesses a double-stranded RNA-dependent ATP-binding site. J Biol Chem 260 8237-8239 Bolovan CA, Sawtell NM, Thompson RL (1994) ICP34.5 mutants of herpes simplex virus type 1 strain 17syn+ are attenuated for neurovirulence in mice and for replication in confluent primary mouse embryo cell cultures. J Virol 68 48-55... 

Zhou A, Paranjape JM, Der SD et al. Interferon action in triply deficient mice reveals the existence of alternative antiviral pathways. Virology 1999 258(2) 435-440. 

THE INTERFERON SYSTEM STUDIES ON THE MOLECULAR MECHANISM OF INTERFERON ACTION... 

Taken together, these results provide additional evidence of the pleiotropic effect of interferon. Although interferon-treated cells exhibited the antiviral state when infected with each of the viruses used throughout this study, the cell responded in different ways to the infection, at least at the level of ribonuclease activity and of the exteni of phosphorylation of P67. In the case of mengo virus the enhanced ribonuclease activity and its location, triggered by the infection may explain the interferon action. The relationship between the expression of the antiviral state and the protein kinase system remains to be demonstrated. 

Lengyel, P., 1982Z , Interferon action Control of RNA processing, translation and degradation, in Protein Biosynthesis in Eukaryotes (R. Perez-Bercoff, ed.), pp. 459-483, Plenum Publishing, New York. 

Samuel, C. E., 1979, Mechanism of interferon action Phosphorylation of protein synthesis initiation factor eIF-2 in interferon treated human cells by a ribosome associated kinase processing site specificity similar to hemin-regulated rabbit reticulocyte kinase, Proc. Natl Acad. Sci. USA 76 600. 

Marcus, P. I., Engelhardt, D. L., Hunt, J. M., and Sekellick, M. J., 1971, Interferon action. Inhibition of vesicular stomatitis virus RNA synthesis induced by virion-bound polymerases, Science 174 593. 

Sen, G. C., 1982, Mechanisms of interferon action Progress toward its understanding, Prog. Nucl. Acid. Res. Mol. Biol. 17 106. 

Taylor, J., 1965, Studies on the mechanism of action of interferon, 1. Interferon action and RNA synthesis in chick embryo fibroblasts infected with Semliki Forest virus. Virology 25 340. 

Weihua X, Kolia V, Kalvakolanu DV (1997) Modulation of interferon action by retinoids. J Biol Chem 272 9742-9748... 

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