Analysis of an orf virus chemokine-binding protein: Shifting ligand specificities among a family of poxvirus viroceptors

Bruce T. Seet, Catherine A. McCaughan, Tracy M. Handel, Andrew Mercer, Craig Brunetti, Douglas McFadden, Stephen B. Fleming

Research output: Contribution to journalArticle

53 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)15137-15142
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number25
DOIs
StatePublished - Dec 9 2003
Externally publishedYes

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Orf virus
Poxviridae
Virus Attachment
Chemokines
Carrier Proteins
Ligands
Granulocyte-Macrophage Colony-Stimulating Factor
CC Chemokines
Leporipoxvirus
Interleukin-2
Parapoxvirus
Proteins
C Chemokines
Orthopoxvirus
Viral Proteins
Protein Binding
Amino Acid Sequence

ASJC Scopus subject areas

  • General

Cite this

Analysis of an orf virus chemokine-binding protein : Shifting ligand specificities among a family of poxvirus viroceptors. / Seet, Bruce T.; McCaughan, Catherine A.; Handel, Tracy M.; Mercer, Andrew; Brunetti, Craig; McFadden, Douglas; Fleming, Stephen B.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 25, 09.12.2003, p. 15137-15142.

Research output: Contribution to journalArticle

Seet, Bruce T. ; McCaughan, Catherine A. ; Handel, Tracy M. ; Mercer, Andrew ; Brunetti, Craig ; McFadden, Douglas ; Fleming, Stephen B. / Analysis of an orf virus chemokine-binding protein : Shifting ligand specificities among a family of poxvirus viroceptors. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 25. pp. 15137-15142.
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