Secreted poxvirus chemokine binding proteins.
Poxviruses encode a variety of immunomodulatory proteins that subvert the cytokine networks of infected hosts. Myxoma virus, a poxvirus pathogen of rabbits, expresses two distinct 35- to 40-kDa secreted glycoproteins that bind a broad spectrum of chemokines. The first of these, designated 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 cellular interferon-gamma receptor but binding studies indicate that purified M-T7 protein also interacts with members of the CXC, CC, and C chemokine families through the conserved heparin-binding domains. The second myxoma protein, M-T1, also called CBP-II, is a member of a larger superfamily of poxvirus proteins that includes related secreted 35-kDa proteins encoded by a wide variety of orthopoxviruses. Deletion analysis of either CBP-I or -II genes within recombinant poxvirus constructs revealed profound alterations in the trafficking of infiltrating leukocytes into virus-infected lesions. It is proposed that the interaction of CBP-I with the conserved heparin-binding domains found on most chemokines represents a novel mechanism for altering multiple chemokine functions in vivo. In summary, CBP-I and CBP-II are the first examples of secreted virus proteins that bind to multiple chemokine family members as part of a strategy to prevent the early phase of inflammatory cell migration into virus-infected tissues.
Lalani
A S
AS
Department of Biochemistry, University of Alberta, Edmonton, Canada.
McFadden
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G
D000818:Animals; D018925:Chemokines / Q000276:immunology / Q000378:metabolism*; D011212:Poxviridae / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011213:Poxviridae Infections / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D018925:Chemokines; D014764:Viral Proteins