Analysis of an interaction between the soluble vaccinia virus-coded type I interferon (IFN)-receptor and human IFN-alpha1 and IFN-alpha2.

The soluble B18R protein coded by vaccinia virus exerts properties of a type I interferon (IFN)-receptor with broad species specificity. We analyzed neutralizing and binding activity of the B18R protein against several recombinant human type I IFNs. The B18R protein inhibited the antiviral potency of IFN-alpha1, IFN-alpha2, IFN-alpha8/1/8, and IFN-omega on human cells. The N-terminal domain of human type I IFN is involved in the high affinity binding to its cellular receptor. To localize the binding domain(s) of IFN with the B18R protein, competition experiments between B18R, and mapped monoclonal antibodies to IFN-alpha1 and IFN-alpha2 were performed. Surprisingly, our data indicated that the contact area between the B18R protein and IFN comprised in addition to the N-terminal region of IFN-molecule also its C-terminal portion. We suggest that this different pattern of interaction with a ligand might determine the ability of B18R protein to bind type I IFNs of different species.