Recent progress in interferon research: molecular mechanisms of regulation, action, and virus circumvention

A complex system of cis regulatory elements exists by which induction of IFN gene expression is initiated in response to a variety of inducers; cis elements also appear to be involved in the down-regulation of IFN production. IFN gene activation or inhibition of expression may be tightly regulated by the specific binding of newly synthesized or modified proteins to be regulatory regions of the IFN genes. IFN itself acts as a potent modulator of multiple cellular activities. By binding to specific cell surface receptors and probable internalization via receptor-mediated endocytosis and transport into the dense chromatin, IFN treatment leads to activation of numerous genes, some of which possess known antiviral or immunoregulatory functions, whereas the function of others remains to be identified. As with the IFN genes themselves, many of the IFN-inducible genes appear to possess complex regulatory mechanisms, including domains for binding of specific trans-acting proteins. To add to this molecular complexity some viruses have successfully developed methods to circumvent, among other mechanisms, the 2',5'-A-mediated system and the P1 protein kinase system.