B18R is a type I interferon (IFN)-binding protein, which is encoded by the B18R open reading frame in the WR (WesternReserve)strain of vaccinia virus. Itis alsoknownasB19RintheCopenhagenstrainofVaccinia. B18R exists in a soluble and a membrane-bound form. As a type I IFN receptor, B18R has a broad species specificity. It has high affinity for human IFN-alpha and also binds rabbit, bovine, rat, pig, and mouse IFN-alpha and IFN-beta. It has been shown that secreted B18R binds to uninfected and infected cells. It presents at the cell surface and protects cells from the antiviral state induced by IFN-alpha and IFN-beta. Binding of soluble recombinant B18R protects cultured cells from IFN and allows vaccinia virus replication.