The induction of phosphorylation of both
protein P1 and
protein synthesis
initiation factor eIF-2 alpha and the inhibition of virus replication were examined in mouse L929 fibroblasts treated with either natural mouse or individual cloned human
interferons (IFN). Natural mouse IFN synthesized in Newcastle disease virus-induced L929 cells and two cloned human leukocyte IFN subspecies synthesized in Escherichia coli,
IFN-alpha D and IFN-alpha A/D, possessed
antiviral activity in L929 cells as measured by single cycle virus yield reduction with both
vesicular stomatitis virus and reovirus. Natural L929 IFN and cloned IFNs, alpha D and alpha A/D, also induced the
protein kinase that catalyzed the phosphorylation of endogenous ribosome-associated
protein P1 and the alpha subunit of purified
initiation factor eIF-2. Two other cloned human IFNs, alpha A and alpha D/A, were poor inducers of both the
antiviral state and the phosphorylation of P1 and
eIF-2 alpha in mouse L929 cells. The ability of individual human IFN-alpha subspecies to induce P1 and
eIF-2 alpha phosphorylation in mouse L929 cells correlated with their ability to induce an
antiviral state. Furthermore, the detailed kinetics of induction, in mouse L929 cells, of P1 and
eIF-2 alpha phosphorylation and of the
antiviral state by the heterologous cloned human IFN-alpha A/D were equivalent to the kinetics of induction by the homologous natural mouse L929 IFN. These results suggest that different subspecies of biologically active IFN induce equivalent
antiviral activities and biochemical changes in mouse L929 cells, and that
protein phosphorylation may play a major role in the
antiviral mechanism of IFN action in mouse L929 fibroblasts.