DIFFERENT RELATIVE ACTIVITIES OF HUMAN CELL-DERIVED INTERFERON-ALPHA SUBTYPES - IFN-ALPHA-8 HAS VERY HIGH ANTIVIRAL POTENCY

Interferon-alpha (IFN-alpha) subtypes were separated by HPLC from the IFN mixtures produced by virus-stimulated human lymphoblastoid cells a nd leukocytes. Together with preparations of lymphoblastoid IFN and re combinant IFN-beta, these were tested in three human tumor cell lines derived from liver, lung, and neuroblasts, Their relative antiviral ac tivities differed markedly: subtype IFN-alpha 8 was the most potent an d IFN-alpha 1 the least, The results were broadly similar in all three cells, with some minor differences. When the same preparations were t ested for inhibition of thymidine incorporation, the relative activiti es were quite different: subtypes IFN-alpha 10, IFN-alpha 17, IFN-alph a 21, and IFN-alpha 5 were now the most active, and IFN-alpha 2 was th e least active, IFN-alpha 1 and IFN-alpha 8 had comparable intermediat e activity, Thus, the differences in activity were not caused by degra dation of some subtypes during their separation, IFN-alpha 8 not only had the greatest antiviral activity but also, like IFN-beta, induced a n antiviral state in U1 mutant cell lines, which lack the tyrosine kin ase, Tyk2, required for signal transduction by other IFN-alpha subtype s.