Abstract
The induction of protein phosphorylation and the inhibition of virus replication by several subspecies of human alpha (leukocyte) interferon (HuIFN-α were examined in human and monkey cells in culture. Five recombinant IFN-α subspecies synthesized in Escherichia coli, IFN-αB, αC, αF, αI, and αJ, all inhibited vesicular stomatitis virus (VSV) replication in both human amnion U and monkey kidney BSC-1 cells. The relative specific antiviral activity varied in the order aI > αB ≅ αF > αC ≅ αJ in both human U and monkey BSC-1 cells. By contrast, the double-stranded RNA (dsRNA)-dependent phosphorylation of ribosome-associated protein P1 was induced in human U cells but not in monkey BSC-1 cells by IFN-αB, αC, αF, αl, and αJ. Furthermore, two forms of P1 phosphorylation were induced in U cells by all five of the IFN-α subspecies: one form was clearly detectable after 2.5 h of IFN treatment, whereas the other phosphorylated form required longer periods of IFN treatment and was superinduced by the addition of actinomycin D following IFN treatment. Using one of the cloned IFN subspecies, αI, the induction of both forms of P1 phosphorylation in human U cells was shown to depend upon the concentration of IFN during treatment. However, similar to BSC-1 cells, protein phosphorylation was not induced by IFN-αI in human fibroblast GM2767A cells although an antiviral state was induced in GM2767A cells. These results suggest that the ability of individual human IFN-α subspecies to induce protein phosphorylation and inhibit virus replication is specified by the host cell rather than the IFN-α subspecies. This conclusion is further supported by the observation that the human recombinant hybrid IFN-α/D inhibited both reovirus and vesicular stomatitis virus (VSV) replication in monkey BSC-1 cells, whereas in human U cells reovirus was virtually unaffected by IFN-αA/D even though VSV replication was fully inhibited.
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