title: Analysis of an orf virus chemokine-binding protein: Shifting ligand specificities among a family of poxvirus viroceptors.
abstract: We identify a secreted chemokine inhibitor encoded by orf virus (ORFV), the prototypic poxvirus of the Parapoxvirus genus, and show that it is related to the poxvirus type II CC-chemokine-binding proteins (CBP-II) produced by members of the Orthopoxvirus and Leporipoxvirus genera. The ORFV chemokine-binding protein (CBP) is functionally similar to the CBP-II proteins in its ability to bind and inhibit many CC-chemokines with high affinity. However, unlike CBP-II, the ORFV CBP also binds with high affinity to lymphotactin, a member of the C-chemokine family, demonstrating that the ORFV CBP possesses an altered binding specificity. Interestingly, the amino acid sequence of ORFV CBP more closely resembles the granulocyte-macrophage colony-stimulating factor/IL-2 inhibitory factor also produced by ORFV, implicating the granulocyte-macrophage colony-stimulating factor/IL-2 inhibitory factor protein as a highly diverged, but related, member of the CBP-II protein family. Notably, these findings suggest that the genes that encode these proteins derive from a common poxvirus ancestral gene that has since been modified in binding specificity during speciation of the poxvirus genera. Overall, these findings illustrate the concept of evolution of viral proteins at the biophysical and molecular interface.
authors.affiliation: Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada N6A 5C1.
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Seet
authors.forename: Catherine A
authors.initials: CA
authors.lastname: McCaughan
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Handel
authors.forename: Andrew
authors.initials: A
authors.lastname: Mercer
authors.forename: Craig
authors.initials: C
authors.lastname: Brunetti
authors.forename: Grant
authors.initials: G
authors.lastname: McFadden
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Fleming
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D000939:Epitopes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009923:Orf virus / Q000378:metabolism*; D010802:Phylogeny; D011212:Poxviridae / Q000235:genetics; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D014764:Viral Proteins / Q000737:chemistry
chemical_list: D018925:Chemokines; D016207:Cytokines; D000939:Epitopes; D007376:Interleukin-2; D008024:Ligands; D014764:Viral Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D002118:Calcium