title: Antiviral protection mechanisms mediated by ginbuna crucian carp interferon gamma isoforms 1 and 2 through two distinct interferon gamma-receptors.
abstract: Fish genomes possess three type II interferon (IFN) genes, ifnγ1, ifnγ2 and ifnγ-related (ifnγrel). The IFNγ-dependent STAT signalling pathway found in humans and mice had not been characterized in fish previously. To identify the antiviral functions and signalling pathways of the type II IFN system in fish, we purified the ifnγ1, ifnγ2 and ifnγrel proteins of ginbuna crucian carp expressed in bacteria and found them to elicit high antiviral activities against crucian carp hematopoietic necrosis virus. We also cloned two distinct ifnγ receptor alpha chain (ifngr1) isoforms, 1 and 2, and stably expressed them in HeLa cells by transfecting the cells with ifngr1-1 or ifngr1-2 cDNA. When receptor transfectants were treated with the ligands in a one-ligand-one-receptor manner (ifnγ1 and ifngr1-2 or ifnγ2 and ifngr1-1), the stat1 protein was phosphorylated at both serine-727 and tyrosine-701 residues. Gel shift mobility analysis and reporter assay clearly showed that the specific ligand-receptor interaction resulted in the binding of the stat1 protein to the GAS element and enhanced transcription. Therefore, the actions of ifnγ1 and ifnγ2 were found to be mediated by a specific receptor for each signalling pathway via a stat1-dependent mechanism.
authors: Nihon University College of Bioresource Sciences 1866, Kameino, Fujisawa, Kanagawa, 252-0880, Japan.
authors: Takeshi
authors: T
authors: Yabu
authors: Hideaki
authors: H
authors: Toda
authors: Yasuhiro
authors: Y
authors: Shibasaki
authors: Kyosuke
authors: K
authors: Araki
authors: Michiaki
authors: M
authors: Yamashita
authors: Hirosi
authors: H
authors: Anzai
authors: Nobuhiro
authors: N
authors: Mano
authors: Yoshikazu
authors: Y
authors: Masuhiro
authors: Shigemasa
authors: S
authors: Hanazawa
authors: Hajime
authors: H
authors: Shiba
authors: Tadaaki
authors: T
authors: Moritomo
authors: Teruyuki
authors: T
authors: Nakanishi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002347:Carps / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D029141:Novirhabdovirus / Q000187:drug effects* / Q000276:immunology; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000821:virology; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D000096743:Interferon gamma Receptor
chemical_list: D000998:Antiviral Agents; D018076:DNA, Complementary; D007371:Interferon-gamma; D020033:Protein Isoforms; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human