Independent evolution of antiviral and growth-modulating activities of interferon

Interferon (IFN) may be an extraordinarily ancient antiviral defense used by animals and plants. In animals, the antiviral properties of IFN may have been rendered redundant in part by the evolution of cell-mediated immunity. Comparative analysis of gene and protein structures, combined with examinations of biological specificities, suggest that IFN-beta and IFN-gamma have evolved new functions that include regulation of hematopoietic cell differentiation. An inspection of the events required for growth control by IFN suggests that this evolution consisted of the addition of an "antiproliferative domain" to a primitive IFN molecule that was previously capable of eliciting only an antiviral response. These evolutionary considerations lead to the speculation that some molecular species of IFN-alpha retain specific and potent biological activities, whereas other species may be losing both target cell specificity and biological potency over time. Important clinical problems, as well as opportunities, are raised by these hypotheses, particularly the problem of toxicity to normal organs resulting from the chronic use of certain cloned interferons at the relatively high doses that may be necessary to compensate for evolutionary alterations in their structure and function.