Mechanism of interferon action: Cloned human leukocyte interferons induce protein kinase and inhibit vesicular stomatitis virus but not reovirus replication in human amnion cells

The induction of protein P, and initiation factor eIF-2 phosphorylation and the inhibition of virus replication were examined in human amnion U cells treated with cloned and natural human leukocyte interferons. Three leukocyte interferons (IFN-a) synthesized in Escherichia coli, αA, al), and αA/D, and natural IFN-α synthesized in Sendai virus-induced leukocytes induced the protein kinase that catalyzes the phosphorylation of ribosome-associated protein P, and purified initiation factor eIF-2. Natural IFN-α and cloned IFNs αA, al), and αA/D also possessed antiviral activity as measured by single cycle virus yield reduction with vesicular stomatitis virus, but not with reovirus, in human amnion U cells. A fourth cloned IFN, αD/A, was a poor inducer both of protein P 1 and eIF-2 phosphorylation and of antiviral activity in U cells. These results establish that cloned as well as natural IFN-a subspecies induce protein P, and eIF-2 phosphorylation in human U cells, and suggest that the induction of protein phosphorylation is not a sufficient condition for the expression of antiviral activity in human cells with viruses such as reovirus which are sensitive to IFN in mouse and monkey cells.