Glycosylation, intraspecies molecular heterogeneity and trans-species activity of mammalian interferons

Abstract

Interferon, a glycoprotein with demonstrated antitumor and antiviral properties, can be obtained from cells of different species and some of these interferons can be effective across species lines. Interpretation of new information provides the raison d'etre of an intergrative model — that the ability to cross, or not cross, species lines lies in the carbohydrate moiety and cross-species biological activity is a property of the polypeptide. When interferon molecules have a defect in glycosylation, limit proteolysis also occurs more readily in biological fluids, further modulating cross-species activity of the polypeptide backbone. While providing the first coherent interpretation of available genetic and biochemical data, the model does not exclude a possible role of differential processing (as between various cell types) of nuclear interferon mRNA transcripts, but this seems unlikely. Apparently, post-translational modification explains both intraspecies interferon molecular heterogeneity as well as the ‘species-barrier’ itself. If this hypothesis is correct, then it should be possible to use animal-derived interferon as the first large scale inexpensive source to treat human diseases. Since interferons may share structural homology with other polypeptides and a common mode of receptor interaction, the hypothesis has wider biomedical interest. Thus, polypeptide hormones may be uncovered in which removal of the sugar prosthetic group results in augmentation of cross-species activity to human.