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Identification of residues in the ectromelia virus gamma interferon-binding protein involved in expanded species specificity

Authors :
R. Mark L. Buller
Anthony A. Nuara
Hongdong Bai
Source :
The Journal of general virology. 88(Pt 1)
Publication Year :
2006

Abstract

Gamma interferon (IFN-γ) production is important in the host response to, and recovery from, infection with Ectromelia virus (ECTV) and Vaccinia virus (VACV). The orthopoxviruses have evolved several mechanisms to subvert the IFN-γ response. IFN-γ-binding protein (IFN-γBP) is a virally encoded homologue of the host IFN-γ receptor that blocks the effects of IFN-γ in the infected host. Unlike the cellular receptors, whose ligand specificity is restricted to their own species, the orthopoxvirus IFN-γBPs bind IFN-γ from several species. The reason for this relaxed specificity has yet to be explained. ECTV, a mouse pathogen, encodes an IFN-γBP that has been shown to inhibit the activity of both human and murine IFN-γ (hIFN-γ and mIFN-γ, respectively). In contrast, the IFN-γBP from VACV is unable to inhibit mIFN-γ, but retains activity against hIFN-γ. To determine which region(s) in the ECTV sequence is responsible for its ability to bind to mIFN-γ with high affinity, a series of chimeric IFN-γBPs, as well as individual point mutants in the ECTV sequence corresponding to the amino acid changes from the VACV sequence, were constructed. The affinities of the chimeric and point mutant IFN-γBPs for mIFN-γ were tested by using surface plasmon resonance and bioassay. By using this strategy, several key residues in the ligand-binding domains of the ECTV sequence have been identified that are responsible for high-affinity binding to mIFN-γ. Substitution of the ECTV residue at these positions in VACV resulted in a dramatic increase in the affinity of the VACV IFN-γBP for mIFN-γ.

Details

ISSN :
00221317
Volume :
88
Issue :
Pt 1
Database :
OpenAIRE
Journal :
The Journal of general virology
Accession number :
edsair.doi.dedup.....a55cd5a53a82f1b388d6bfe269158358