Vaccinia virus B18R gene encodes a type I interferon-binding protein that blocks interferon α transmembrane signaling

Abstract

Poxviruses encode a large number of proteins that attenuate the inflammatory and immune responses to infection. In this report we demonstrate that a number of orthopoxviruses express a type I interferon (IFN)binding protein, which is encoded by the B18R open reading frame in the WR strain of vaccinia virus. The B18R protein has significant regions of homology with the α subunits of the mouse, human, and bovine type I IFN receptors, bound human IFNα2 with high affinity, and inhibited transmembrane signaling as demonstrated by inhibition of Fc receptor factor γ1/γ2 and interferon- stimulated gene factor-3 formation as well as inhibition of the IFNα antiviral response. Among viral host response modifiers, the B18R protein is unique inasmuch as it exists as a soluble extracellular as well as a cell surface protein and thus should effectively block both autocrine and paracrine functions of IFN.