title: Functional characterizations of IPS-1 in CIK cells: Potential roles in regulating IFN-I response dependent on IRF7 but not IRF3.
abstract: IPS-1, as the sole adaptor of RIG-I and MDA5, plays a central role in innate antiviral immunity. In this study, we investigated potential roles of IPS-1 in innate immunity and the domain-requirement of IPS-1 for its signaling in grass carp (Ctenopharyngodon idella). Overexpression experiment showed that CiIPS-1 mediated IFN-I signal possibly dependent on CiIRF7 but not CiIRF3. Post GCRV challenge, CiIPS-1 could enhance antiviral immune responses. CARD and TM domains were crucial for antiviral function of CiIPS-1, and TRAF motif played an assistant role. PRO domain seemed as a negative regulator but was pivotal for the initiation of CiIFN-I and CiMx1. Post viral/bacterial PAMPs stimulation, CiIPS-1-mediated signaling was tightly controlled. CARD domain of CiIPS-1 could significantly elicit poly I:C/LPS/PGN-mediated signaling. PRO domain negatively regulated CiIRF7 and CiIFN-I but was indispensable for inductions of CiMx1 and CiIL-1β. TRAF motif and TM domain regulated the signaling presumably in a cooperative fashion. Post poly I:C stimulation, TRAF motif negatively regulated CiIRF7, CiIFN-I and CiIL-1β at a relative early time while TM domain functioned at a relative late time. TRAF motif was indispensable for the production of CiMx1, while TM domain slightly negatively regulated the expression. Post LPS and PGN stimulation, TRAF motif excited an assistant and persistent negative role on CiIFN-I, CiIRF7 and CiIL-1β induction, but was crucial for induction of CiMx1. TM domain slightly negatively regulated LPS- and PGN-triggered signaling. Taken together, CiIPS-1 not only exerted important functions in antiviral immune response but also participated in viral/bacterial PAMPs-triggered immune response which was tightly controlled to prevent harmful effects resulting from excessive activation. This study provided novel insights into the pivotal role of IPS-1 in innate immunity.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Feng
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Chunrong
authors.initials: C
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors.forename: Lanjie
authors.initials: L
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China; College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China; Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070, China. Electronic address: sujianguo2015@163.com.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Su
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002347:Carps / Q000276:immunology*; D002478:Cells, Cultured; D005393:Fish Diseases / Q000276:immunology / Q000821:virology; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000276:immunology; D010457:Peptidoglycan / Q000276:immunology; D017434:Protein Structure, Tertiary; D012087:Reoviridae / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D064547:Myxovirus Resistance Proteins; D010457:Peptidoglycan; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
keywords: Functional characteristics; Grass carp (Ctenopharyngodon idella); Grass carp reovirus; IPS-1