Interferon: Current concepts of mechanisms of action

Abstract

Almost 30 years ago Isaacs and Lindenmann [1] discovered that the supernatant obtained from cells incubated with heat-inactivated influenza virus contained a substance capable of preventing the growth of active virus. This substance, named interferon (IFN), was later shown to be composed of a system of structurally related proteins that act directly on the target cells, not on the virus, and are produced by many types of animal cells in response to various external stimuli (e.g., viruses, certain types of double-stranded RNA, antigens, or mitogens). Three classes of IFNs have been described that differ in their amino acid sequences, as well as immunochemical and physicochemical properties: alpha (leukocyte), beta (fibroblast), and gamma (immune) IFN. Alpha and beta IFNs have also been designated as type I (acid-stable) and gamma IFN as type II (acid-labile). The alpha IFNs, which are produced by a variety of different cells including macrophages, null cells (non-B- and non-T-lymphocytes) and transformed B-cell lines, are a family of at least 14 species that share a 75% or greater amino acid sequence homology. Beta IFN, which shares ca30% amino acid sequence homology with alpha IFNs, is produced mainly by fibroblasts and epithelial cells, but may also be produced by human tumor cells derived from leukocytes (e.g., the Namalwa cell line). Gamma IFN is predominantly a product of T-cells and natural killer (NK) cells and shares little homology with type I IFNs.