title: Identification of DreI as an antiviral factor regulated by RLR signaling pathway.
abstract: BACKGROUND
  Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) had been demonstrated to prime interferon (IFN) response against viral infection via the conserved RLR signaling in fish, and a novel fish-specific gene, the grass carp reovirus (GCRV)-induced gene 2 (Gig2), had been suggested to play important role in host antiviral response.
  
  
  RESULTS
  In this study, we cloned and characterized zebrafish Gig2 homolog (named Danio rerio Gig2-I, DreI), and revealed its antiviral role and expressional regulation signaling pathway. RT-PCR, Western blot and promoter activity assay indicate that DreI can be induced by poly I:C, spring viremia of carp virus (SVCV) and recombinant IFN (rIFN), showing that DreI is a typical ISG. Using the pivotal signaling molecules of RLR pathway, including RIG-I, MDA5 and IRF3 from crucian carp, it is found that DreI expression is regulated by RLR cascade and IRF3 plays an important role in this regulation. Furthermore, promoter mutation assay confirms that the IFN-stimulated regulatory elements (ISRE) in the 5' flanking region of DreI is essential for its induction. Finally, overexpression of DreI leads to establish a strong antiviral state against SVCV and Rana grylio virus (RGV) infection in EPC (Epithelioma papulosum cyprinid) cells.
  
  
  CONCLUSIONS
  These data indicate that DreI is an antiviral protein, which is regulated by RLR signaling pathway.
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Wuhan Center for Developmental Biology, Institute of Hydrobiology, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Sun
authors.forename: Yi-Bing
authors.initials: YB
authors.lastname: Zhang
authors.forename: Jian-Fang
authors.initials: JF
authors.lastname: Gui
authors.forename: Qi-Ya
authors.initials: QY
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology; D001483:Base Sequence; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs; D011070:Poly I-C / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D020365:RNA Helicases / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D050821:Transcription Factor Brn-3C / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D018398:Homeodomain Proteins; D050821:Transcription Factor Brn-3C; D029961:Zebrafish Proteins; C574009:gig2i protein, zebrafish; D020365:RNA Helicases; D011070:Poly I-C