SECRETED POXVIRUS CHEMOKINE BINDING-PROTEINS

Poxviruses encode a variety of immunomodulatory proteins that subvert the cytokine networks of infected hosts, Myxoma virus, a poxvirus path ogen of rabbits, expresses two distinct 35- to 40-kDa secreted glycopr oteins that bind a broad spectrum of chemokines. The first of these, d esignated M-T7, is encoded by the T7 gene and is the first example of what is here referred to as type-I chemokine binding protein (CBP-I), M-T7 was initially discovered as a secreted viral homologue of cellula r interferon-gamma receptor but binding studies indicate that purified M-T7 protein also interacts with members of the CXC, CC, and C chemok ine families through the conserved heparin-binding domains, The second myxoma protein, M-T1, also called CBP-II, is a member of a larger sup erfamily of poxvirus proteins that includes related secreted 35-kDa pr oteins encoded by a wide variety of ortho-poxviruses. Deletion analysi s of either CBP-I or -II genes within recombinant poxvirus constructs revealed profound alterations in the trafficking of infiltrating leuko cytes into virus-infected lesions, It is proposed that the interaction of CBP-I with the conserved heparin-binding domains found on most che mokines represents a novel mechanism for altering multiple chemokine f unctions in vivo. In summary, CBP-I and CBP-II are the first examples of secreted virus proteins that bind to multiple chemokine family memb ers as part of a strategy to prevent the early phase of inflammatory c ell migration into virus-infected tissues.