title: Evidence for Paralichthys olivaceus IFITM1 antiviral effect by impeding viral entry into target cells.
abstract: Interferon-inducible transmembrane (IFITM) protein family is novel viral restriction factors with representative transmembrane structure. These proteins also exist in fish, however, their roles in the innate immune response remain unknown. Here, we report a characterization of teleost IFITM1 from flounder Paralichthys olivaceus (PoIFITM1), which exhibits conserved structure characteristic of the IFITM family but comprises a relatively longer N-terminal region. The expression and promoter activity of PoIFITM1 are markedly induced by aquatic animal viruses: Rana grylio virus (RGV) and Scophthalmus maximus rhabdovirus (SMRV). Overexpression and siRNA-mediated knockdown demonstrate that PoIFITM1 exhibits strong antiviral effects against both DNA virus (RGV) and RNA virus (SMRV), expanding the spectrum of viruses inhibited by IFITM proteins. Further analysis shows that PoIFITM1 suppresses viral entry into host cells, confirming that the IFITM-mediated restriction is conserved from lower vertebrates to mammals. Deletion mutagenesis reveals that PoIFITM1 exerts antiviral activity by targeting to Golgi complex and the N-terminal region is required for its subcellular localization, which is not observed in other known IFITM family members. Our current data provide the first evidence that IFITM1 functions as a key effector of the innate immune to restrict virus replication in lower vertebrates, through the action of impeding viral entry.
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Donghu South Road 7, Wuhan 430072, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhu
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Lei
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; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D000998:Antiviral Agents; D001483:Base Sequence; D002478:Cells, Cultured; D005432:Flounder / Q000196:embryology / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D007113:Immunity, Innate; D007497:Iridoviridae / Q000502:physiology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D012209:Rhabdoviridae / Q000502:physiology*; D053586:Virus Internalization; D014779:Virus Replication / Q000502:physiology
chemical_list: D000943:Antigens, Differentiation; D000998:Antiviral Agents; C062010:leu-13 antigen
keywords: Antiviral effect; Golgi localization; Paralichthys olivaceus interferon-inducible transmembrane 1 (PoIFITM1); Rana grylio virus (RGV); Scophthalmus maximus rhabdovirus (SMRV)