Vaccinia Virus-Encoded Cytokine Receptor Binds and Neutralizes Chicken Interferon-γ

Abstract To counteract the host immune response, poxviruses have evolved secreted factors that bind cytokines and thereby neutralize their biological activities. The vaccinia virus B8R gene encodes a protein that neutralizes interferon-γ (IFN-γ) from several mammals including man, cow, rat, and rabbit but not mice. We now report that the activity of the B8R gene product is not restricted to cytokines of mammals: it also efficiently neutralized chicken IFN-γ. B8R blocked chicken IFN-γ-mediated induction of guanylate binding protein RNA in the chicken fibroblast cell line CEC-32 and secretion of nitric oxide in HD-11 cells. Radiolabeled baculovirus-expressed B8R efficiently bound to immobilized recombinant chicken IFN-γ. Scatchard analysis revealed a binding constant of chicken IFN-γ to B8R of approximately 0.5 nM. A mutant form of chicken IFN-γ which lacks the 18 C-terminal amino acids and which has lost more than 99% of its biological activity was able to block the IFN-γ-neutralizing effect of B8R. Binding studies showed that the mutant protein bound radiolabeled B8R only about threefold less well than wild-type chicken IFN-γ but failed to compete with wild-type chicken IFN-γ for binding to the cellular receptor. These results suggest that the extreme C terminus of chicken IFN-γ is crucial for binding to its cellular receptor but less important for recognition by the viral cytokine receptor.