title: The P Protein of Spring Viremia of Carp Virus Negatively Regulates the Fish Interferon Response by Inhibiting the Kinase Activity of TANK-Binding Kinase 1.
abstract: Spring viremia of carp virus (SVCV) is an efficient pathogen causing high mortality in the common carp. Fish interferon (IFN) is a powerful cytokine enabling host cells to establish an antiviral response; therefore, the strategies that SVCV uses to avoid the cellular IFN response were investigated. Here, we report that the SVCV P protein is phosphorylated by cellular TANK-binding kinase 1 (TBK1), which decreases IFN regulatory factor 3 (IRF3) phosphorylation and suppresses IFN production. First, overexpression of P protein inhibited the IFN promoter activation induced by SVCV and the IFN activity activated by the mitochondrial antiviral signaling protein (MAVS) although TBK1 activity was not blocked by P protein. Second, P protein colocalized and interacted with TBK1. Dominant negative experiments suggested that the TBK1 N-terminal kinase domain interacted with P protein and was essential for P protein and IRF3 phosphorylation. Finally, P protein overexpression reduced the IRF3 phosphorylation activated by TBK1 and reduced host cellular ifn transcription. Collectively, our data demonstrated that the SVCV P protein is a decoy substrate for the host phosphokinase TBK1, preventing IFN production and facilitating SVCV replication.
  
  
  OBJECTIVE
  TBK1 is a pivotal phosphokinase that activates host IFN production to defend against viral infection; thus, it is a potential target for viruses to negatively regulate IFN response and facilitate viral evasion. We report that the SVCV P protein functions as a decoy substrate for cellular TBK1, leading to the reduction of IRF3 phosphorylation and suppression of IFN expression. These findings reveal a novel immune evasion mechanism of SVCV.
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Long-Feng
authors.initials: LF
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhao-Xi
authors.initials: ZX
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China yzhang@ihb.ac.cn.
authors.forename: Yong-An
authors.initials: YA
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002347:Carps / Q000235:genetics / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D005393:Fish Diseases / Q000201:enzymology / Q000276:immunology* / Q000821:virology*; D029941:Fish Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D007372:Interferons / Q000096:biosynthesis* / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology*; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D018116:Vesiculovirus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000662:veterinary / Q000821:virology; D014779:Virus Replication
chemical_list: D029941:Fish Proteins; D010750:Phosphoproteins; D015678:Viral Structural Proteins; D007372:Interferons; D017346:Protein Serine-Threonine Kinases