ABSTRACT
I. INTRODUCTION Interferons (IFNs), which were independently discovered by two groups in the 1950s (1,2), are proteins capable of interfering with the viral infection of cells. Their discovery culminated many years of study on the basis for viral interference. Besides antiviral activity, the diverse biological actions of these cytokines also include inhibition of the proliferation of normal and transformed cells, regulation of differentiation, host responses to various pathogens, and modulation of the immune system (including activation of natural killer cells and macrophages). The human type I IFNs include 15 IFN-a subtypes, one IFN-0 subtype, and two IFN-w subtypes. Type I IFNs are acid stable, have similar protein structure and biological activities, bind and transduce signals through a common multiprotein cell surface receptor, are induced in response to viral and other inducers, and share a common gene locus on human chromosome 9. In contrast, type II IFN (or IFN-y) is acid-labile and differs from type I IFNs in many of the above respects except that it shares similar biological actions. However, there are differences in biological potency of type I and type II IFNs. For example, type II IFN is considered more active in immunomodulation than type I IFN. In addition, the biological specific activities for the different type I IFN subtypes can vary by as much as three orders of magnitude on a logo scale.
