Synergistic antiviral and antiproliferative activities of Escherichia coli-derived human alpha, beta, and gamma interferons

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Abstract
The antiviral and antiproliferative effects of highly purified E. coli-derived human interferons (IFN) were examined in human melanoma cells (Hs294T). Antiproliferative activity was monitored by measuring inhibition of cell multiplication, and antiviral activity was determined by inhibition of herpes simplex virus type 1 replication. Treatment of cells with IFN-.gamma. in combination with IFN-.alpha.A or IFN-.beta.1 resulted in potentiation of both antiproliferative and antiviral activities. Combination treatments composed of IFN-.alpha.A and IFN.beta.1 yielded inconsistent results. Some combinations reflected additive responses, whereas others were antagonistic. To examine correlations betweem IFN-induced biological activities and interactions of the different IFN with cell surface receptors, in vivo [35S]methionine-labeled IFN-.alpha.A was prepared. Binding studies indicated the presence of 2980 .+-. 170 receptors per cell, each with an apparent Kd of (8.4 .+-. 1.3) .times. 10-11 M. Results from competitive binding studies suggested that Hs294T cells possess at least 2 types of IFN receptors: one which binds IFN-.alpha.A and IFN-.beta.1 and another to which IFN-.gamma. binds.