{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T08:06:25Z","timestamp":1771661185024,"version":"3.50.1"},"reference-count":28,"publisher":"Microbiology Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,1,1]]},"abstract":"Gamma interferon (IFN-\u03b3<\/jats:italic>) production is important in the host response to, and recovery from, infection with Ectromelia virus<\/jats:italic> (ECTV) and Vaccinia virus<\/jats:italic> (VACV). The orthopoxviruses have evolved several mechanisms to subvert the IFN-\u03b3<\/jats:italic> response. IFN-\u03b3<\/jats:italic>-binding protein (IFN-\u03b3<\/jats:italic>BP) is a virally encoded homologue of the host IFN-\u03b3<\/jats:italic> receptor that blocks the effects of IFN-\u03b3<\/jats:italic> in the infected host. Unlike the cellular receptors, whose ligand specificity is restricted to their own species, the orthopoxvirus IFN-\u03b3<\/jats:italic>BPs bind IFN-\u03b3<\/jats:italic> from several species. The reason for this relaxed specificity has yet to be explained. ECTV, a mouse pathogen, encodes an IFN-\u03b3<\/jats:italic>BP that has been shown to inhibit the activity of both human and murine IFN-\u03b3<\/jats:italic> (hIFN-\u03b3<\/jats:italic> and mIFN-\u03b3<\/jats:italic>, respectively). In contrast, the IFN-\u03b3<\/jats:italic>BP from VACV is unable to inhibit mIFN-\u03b3<\/jats:italic>, but retains activity against hIFN-\u03b3<\/jats:italic>. To determine which region(s) in the ECTV sequence is responsible for its ability to bind to mIFN-\u03b3<\/jats:italic> with high affinity, a series of chimeric IFN-\u03b3<\/jats:italic>BPs, 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-\u03b3<\/jats:italic>BPs for mIFN-\u03b3<\/jats:italic> 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-\u03b3<\/jats:italic>. Substitution of the ECTV residue at these positions in VACV resulted in a dramatic increase in the affinity of the VACV IFN-\u03b3<\/jats:italic>BP for mIFN-\u03b3<\/jats:italic>.<\/jats:p>","DOI":"10.1099\/vir.0.82324-0","type":"journal-article","created":{"date-parts":[[2006,12,15]],"date-time":"2006-12-15T01:42:25Z","timestamp":1166146945000},"page":"51-60","source":"Crossref","is-referenced-by-count":9,"title":["Identification of residues in the ectromelia virus gamma interferon-binding protein involved in expanded species specificity"],"prefix":"10.1099","volume":"88","author":[{"given":"Anthony A.","family":"Nuara","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Saint Louis University Health Sciences Center, St Louis, MO 63104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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