Interferon induction: regulation by both virus and cell.

Both the virus and its host cell play significant roles in the regulation of interferon (IFN) induction and production. The virus exerts a regulatory effect through variation in its capacity to deliver an IFN inducer molecule in the form of dsRNA, and by suppressing activation of the IFN gene(s) or their subsequent expression. Regulation of IFN induction by genetically closely related viruses may encompass a 10,000-fold range of IFN yields. Viruses that fail to induce IFN express a dominant phenotype in that they suppress IFN induction in cells otherwise programed to produce IFN. The loss of the IFN induction-suppressing phenotype through non-temperature-sensitive mutations is accompanied by the acquisition of IFN inducibility from an otherwise latent state. The cell regulates production of IFN through genetically programed events as part of the developmental process in embryos, and through physiological changes that occur during incubation in vitro. In the developing chicken embryo, the acquisition of IFN inducibility may span a 1,000-fold range of IFN yields, and appears as a time-dependent process proceeding uninterrupted from in ovo to in vitro culture. Populations of established cell lines contain subpopulations (clones) that can differ 10-fold from the mean IFN yielding capacity of the parent, and may undergo physiological changes upon "aging" in vitro that also span a 10-fold range of IFN yields. During development, and most likely as a result of physiological changes brought on by aging in vitro, IFN regulatory factors themselves are regulated. This report reviews the regulation of IFN induction and production with vesicular stomatitis virus (VSV) as a model virus, and primary chick embryo cells and an established line of mouse L cells as model host cells to define systematically the extent and manner in which the virus and cell regulate IFN induction and production.