Studies with Pure Mouse Ehrlich Ascites Tumor Interferons α and β: Patterns of Induction of (2′-5′) (A)nSynthetase and of a Double-Stranded RNA-Dependent Protein Kinase in Mouse Cells and Human Cells

Publisher Website
Google Scholar
Abstract
The N-terminal sequences of mouse Ehrlich ascites tumor cell IFNβ (35,000–40,000 daltons) and IFNα (20,000 daltons) differ in 18 out of 20 positions. Furthermore, these two IFN species show little immunological cross reactivity. We treated mouse L929 cells and human HeLa S3 cells with essentially pure mouse IFNα or IFNβ or both at various concentrations and for various lengths of time. From the treated cells we prepared extracts and compared in these the activities of (2′-5′)(A)n synthetase, an enzyme that was earlier shown to be induced by partially purified IFN preparations. The effects of treatment of mouse L929 cells with pure IFNα or IFNβ on (2′-5′) (A)n accumulation in the cell extracts were very similar both in respect to the dependence on the length of exposure of the cells to the IFNs and on IFN concentration. Treatment with both IFNα and IFNβ at concentrations resulting in only partial induction of the enzyme led to an additive rather than to a synergistic effect. The maximal level of enzyme induced was the same in cells treated with high concentrations of IFNα or IFNβ or both. Mouse IFNα was as active as IFNβ in inducing a double-stranded RNA-dependent protein kinase in mouse L cells. The treatment of HeLa S3 cells with IFNβ did not affect the accumulation of (2′-5′) (A)n in their extracts whereas treatment with IFNα boosted the accumulation though to a lesser extent than in the case of mouse L cells. These results are in line with the finding that mouse IFNα can, but mouse IFNβ cannot convert HeLa S3 cells into the antiviral state and also with the more pronounced homology in N-terminal sequence between mouse IFNα and a human (lymphoblastoid) IFNα than between mouse IFNβ and a human IFNβ.