VACCINIA VIRUS B18R GENE ENCODES A TYPE-I INTERFERON-BINDING PROTEIN THAT BLOCKS INTERFERON-ALPHA TRANSMEMBRANE SIGNALING

Poxviruses encode a large number of proteins that attenuate the inflam matory and immune responses to infection, In this report we demonstrat e that a number of orthopoxviruses express a type I interferon (IFN)-b inding protein, which is encoded by the Dish open reading frame in the WR strain of vaccinia virus, The B18R protein has significant regions of homology with the alpha subunits of the mouse, human, and bovine t ype I IFN receptors, bound human IFN alpha 2 with high affinity, and i nhibited transmembrane signaling as demonstrated by inhibition of Fc r eceptor factor gamma 1/gamma 2 and interferon-stimulated gene factor-3 formation as well as inhibition of the IFN alpha antiviral response, Among viral host response modifiers, the B18R protein is unique inasmu ch as it exists as a soluble extracellular as well as a cell surface p rotein and thus should effectively block both autocrine and paracrine functions of IFN.