title: An interferon-gamma-binding protein of novel structure encoded by the fowlpox virus.
abstract: Poxviruses have evolved various strategies to counteract the host immune response, one of which is based on the expression of soluble cytokine receptors. Using various biological assays, we detected a chicken interferon-gamma (chIFN-gamma)-neutralizing activity in supernatants of fowlpox virus (FPV)-infected cells that could be destroyed by trypsin treatment. Secreted viral proteins were purified by affinity chromatography using matrix-immobilized chIFN-gamma, followed by two-dimensional gel electrophoresis. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis indicated that the viral IFN-gamma-binding protein in question was encoded by the FPV gene 016. The chicken IFN-gamma binding and neutralizing activity of the recombinant FPV016 protein was confirmed using supernatants of cells infected with a recombinant vaccinia virus that lacked its own IFN-gamma-binding protein but instead expressed the FPV016 gene. The FPV016 gene product also neutralized the activity of duck and human IFN-gamma but failed to neutralize the activity of mouse and rat IFN-gamma. Unlike previously known cellular and poxviral IFN-gamma receptors, which all contain fibronectin type III domains, the IFN-gamma-binding protein of FPV contains an immunoglobulin domain. Remarkably, it exhibits no significant homology to any known viral or cellular protein. Because IFN-gamma receptors of birds have not yet been characterized at the molecular level, the possibility remains that FPV016 represents a hijacked chicken gene and that avian and mammalian IFN-gamma receptors have fundamentally different primary structures.
authors.affiliation: Department of Virology, University of Freiburg, D-79104 Freiburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Puehler
authors.forename: Heike
authors.initials: H
authors.lastname: Schwarz
authors.forename: Barbara
authors.initials: B
authors.lastname: Waidner
authors.forename: Jorn
authors.initials: J
authors.lastname: Kalinowski
authors.forename: Bernd
authors.initials: B
authors.lastname: Kaspers
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D002645:Chickens; D002845:Chromatography; D015180:Electrophoresis, Gel, Two-Dimensional; D005347:Fibroblasts / Q000378:metabolism; D005587:Fowlpox virus / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D007525:Isoelectric Focusing; D051379:Mice; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011784:Quail; D012313:RNA / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D014357:Trypsin / Q000494:pharmacology; D014616:Vaccinia virus / Q000235:genetics; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D014764:Viral Proteins; C472776:gene 016 protein, Fowlpox virus; D009569:Nitric Oxide; D012313:RNA; D007371:Interferon-gamma; D014357:Trypsin