Vaccinia virus-encoded cytokine receptor binds and neutralizes chicken interferon-gamma.
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-gamma (IFN-gamma) 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-gamma. B8R blocked chicken IFN-gamma-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-gamma. Scatchard analysis revealed a binding constant of chicken IFN-gamma to B8R of approximately 0.5 nM. A mutant form of chicken IFN-gamma 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-gamma-neutralizing effect of B8R. Binding studies showed that the mutant protein bound radiolabeled B8R only about threefold less well than wild-type chicken IFN-gamma but failed to compete with wild-type chicken IFN-gamma for binding to the cellular receptor. These results suggest that the extreme C terminus of chicken IFN-gamma is crucial for binding to its cellular receptor but less important for recognition by the viral cytokine receptor.
Institut für Medizinische Mikrobiologie und Hygiene, University of Freiburg, Freiburg, 79008, Germany.
F
F
Puehler
K C
KC
Weining
J A
JA
Symons
G L
GL
Smith
P
P
Staeheli
D000818:Animals; D002460:Cell Line; D002645:Chickens; D019204:GTP-Binding Proteins / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D018121:Receptors, Cytokine / Q000378:metabolism*; D014616:Vaccinia virus / Q000378:metabolism*
D018121:Receptors, Cytokine; D009569:Nitric Oxide; D007371:Interferon-gamma; D019204:GTP-Binding Proteins