title: Spring Viremia of Carp Virus N Protein Suppresses Fish IFNφ1 Production by Targeting the Mitochondrial Antiviral Signaling Protein.
abstract: For a virus to replicate efficiently, it must try and inhibit host IFN expression because IFN is an important host defense at early stages after viral infection. For aquatic viruses, the mechanisms used to escape the hosts IFN system are still unclear. In this study, we show that the N protein of spring viremia of carp virus (SVCV) inhibits zebrafish IFNφ1 production by degrading the mitochondrial antiviral signaling protein (MAVS). First, the upregulation of IFNφ1 promoter activity stimulated by polyinosinic:polycytidylic acid, retinoic acid-inducible gene I (RIG-I) or MAVS was suppressed by the SVCV infection. However, the upregulation by the downstream factor of the RIG-I-like receptor signaling pathway, TANK-binding kinase 1, was not affected. Notably, at the protein level, MAVS decreased remarkably when cells were infected with SVCV. Second, consistent with the result of the SVCV infection, overexpression of the N protein of SVCV blocked the IFNφ1 transcription activated by MAVS and downregulated MAVS expression at the protein level but not at the mRNA level. Further analysis demonstrated that the N protein targeted MAVS for K48-linked ubiquitination, which promoted the degradation of MAVS. These data indicated that fish MAVS could be degraded by the N protein of SVCV through the ubiquitin-proteasome pathway. To our knowledge, this is the first article of a fish RIG-I-like receptor pathway interfered by an aquatic virus in an ubiquitin-proteasome manner, suggesting that immune evasion of a virus also exists in lower vertebrates.
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, China;
authors.forename: Long-Feng
authors.initials: LF
authors.lastname: Lu
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China;
authors.forename: Shun
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, China;
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Lu
authors.affiliation: Research Division, Clear Spring Foods, Inc., Buhl, ID 83316; and.
authors.forename: Scott E
authors.initials: SE
authors.lastname: LaPatra
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, China;
authors.forename: Nu
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China.
authors.forename: Xu-Jie
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China;
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Chen
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China;
authors.forename: Pin
authors.identifier: 0000-0002-9492-2940
authors.initials: P
authors.lastname: Nie
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; yzhang@ihb.ac.cn.
authors.forename: Yong-An
authors.identifier: 0000-0002-9956-3879
authors.initials: YA
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002347:Carps; D002460:Cell Line; D000071457:DEAD Box Protein 58 / Q000378:metabolism*; D004847:Epithelial Cells / Q000502:physiology* / Q000821:virology; D057131:Immune Evasion; D007109:Immunity; D007372:Interferons / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D019590:Nucleocapsid Proteins / Q000276:immunology*; D012209:Rhabdoviridae / Q000276:immunology*; D018353:Rhabdoviridae Infections / Q000276:immunology*; D015398:Signal Transduction; D015533:Transcriptional Activation; D054875:Ubiquitination; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000600526:MAVS protein, zebrafish; D019590:Nucleocapsid Proteins; D029961:Zebrafish Proteins; C543713:interferon phi1, zebrafish; D007372:Interferons; D000071457:DEAD Box Protein 58