Interferon-gamma can remain on the cell surface during the induction of the antiviral state.

The antiviral activity of cell-associated, non-elutable recombinant human gamma interferon (rHuIFN-gamma) was neutralized by antibody. The neutralization of cell-associated rHuIFN-gamma was maximal through 2 h (60-100%) and declined through 8 h (20-40%). Concomitantly, the antiviral activity of cell-associated [Met-Gln-Asp-Pro]-rHuIFN-gamma was sensitive to trypsin digestion over the same time period. However, the cell-associated antiviral activity of [Cys-Tyr-Cys]-rHuIFN-gamma remained sensitive to trypsin through 8 h. Neutralization of cell-associated rHuIFN-gamma by antibodies to the N-terminal end of HuIFN-gamma suggests that the N-terminal end(s) of cell-associated rHuIFN-gamma is directed outward from the receptor. Further, immunoprecipitation of radio-labelled rHuIFN-gamma by antibody alone suggests that biologically active rHuIFN-gamma is an oligomer. Taken together, these studies suggest that neutralization of cell-associated rHuIFN-gamma is probably due to divalent binding of antibody to or between rHuIFN-gamma in receptors on the cell surface. Also, our studies indicate that rHuIFN-gamma can remain associated with the cell surface during the induction of the antiviral state (AVS) and that binding of antibody to cell-associated rHuIFN-gamma inhibits the molecular events responsible for induction of the AVS.