Different Relative Activities of Human Cell-Derived Interferon-α Subtypes: IFN-α8 Has Very High Antiviral Potency

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Abstract
Interferon-α (IFN-α) subtypes were separated by HPLC from the IFN mixtures produced by virus-stimulated human lymphoblastoid cells and leukocytes. Together with preparations of lymphoblastoid IFN and recombinant IFN-β, these were tested in three human tumor cell lines derived from liver, lung, and neuroblasts. Their relative antiviral activities differed markedly: subtype IFN-α8 was the most potent and IFN-αl the least. The results were broadly similar in all three cells, with some minor differences. When the same preparations were tested for inhibition of thymidine incorporation, the relative activities were quite different: subtypes IFN-α10, IFN-αl7, IFN-2α1, and IFN-α5 were now the most active, and IFN-α2 was the least active. IFN-αl and IFN-α8 had comparable intermediate activity. Thus, the differences in activity were not caused by degradation of some subtypes during their separation. IFN-α8 not only had the greatest antiviral activity but also, like IFN-β, induced an antiviral state in Ul mutant cell lines, which lack the tyrosine kinase, Tyk2, required for signal transduction by other IFN-α subtypes.