1887

Abstract

Semaphorins are a large, phylogenetically conserved family of proteins that are involved in a wide range of biological processes including axonal steering, organogenesis, neoplastic transformation, as well as immune responses. In this study, a novel semaphorin homologue gene belonging to the Singapore grouper iridovirus (SGIV), ORF155R (termed ), was cloned and characterized. The coding region of is 1728 bp in length, encoding a predicted protein with 575 aa. SGIV-sema contains a ~370 aa N-terminal Sema domain, a conserved plexin-semaphorin-integrin (PSI) domain, and an immunoglobulin (Ig)-like domain near the C terminus. SGIV-sema is an early gene product during viral infection and predominantly distributed in the cytoplasm with a speckled and clubbed pattern of appearance. Functionally, SGIV-sema could promote viral replication during SGIV infection , with no effect on the proliferation of host cells. Intriguingly, ectopically expressed SGIV-sema could alter the cytoskeletal structure of fish cells, characterized by a circumferential ring of microtubules near the nucleus and a disrupted microfilament organization. Furthermore, SGIV-sema was able to attenuate the cellular immune response, as demonstrated by decreased expression of inflammation/immune-related genes such as IL-8, IL-15, TNF-α and mediator of IRF3 activation (MITA), in SGIV-sema-expressing cells before and after SGIV infection. Ultimately, our study identified a novel, functional SGIV gene that could regulate cytoskeletal structure, immune responses and facilitate viral replication.

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2014-05-01
2020-01-24
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References

  1. Alcami A. , Koszinowski U. H. . ( 2000; ). Viral mechanisms of immune evasion. . Immunol Today 21:, 447–455. [CrossRef] [PubMed]
    [Google Scholar]
  2. Bugert J. J. , Darai G. . ( 2000; ). Poxvirus homologues of cellular genes. . Virus Genes 21:, 111–133. [CrossRef] [PubMed]
    [Google Scholar]
  3. Chisholm A. D. . ( 2008; ). Semaphorin signaling in morphogenesis: found in translation. . Genes Dev 22:, 955–959. [CrossRef] [PubMed]
    [Google Scholar]
  4. Comeau M. R. , Johnson R. , DuBose R. F. , Petersen M. , Gearing P. , VandenBos T. , Park L. , Farrah T. , Buller R. M. . & other authors ( 1998; ). A poxvirus-encoded semaphorin induces cytokine production from monocytes and binds to a novel cellular semaphorin receptor, VESPR. . Immunity 8:, 473–482. [CrossRef] [PubMed]
    [Google Scholar]
  5. Conrotto P. , Valdembri D. , Corso S. , Serini G. , Tamagnone L. , Comoglio P. M. , Bussolino F. , Giordano S. . ( 2005; ). Sema4D induces angiogenesis through Met recruitment by Plexin B1. . Blood 105:, 4321–4329. [CrossRef] [PubMed]
    [Google Scholar]
  6. Cui H. , Yan Y. , Wei J. , Hou Z. , Huang Y. , Huang X. , Qin Q. . ( 2011a; ). Cloning, characterization, and expression analysis of orange-spotted grouper (Epinephelus coioides) ILF2 gene (EcILF2). . Fish Shellfish Immunol 30:, 378–388. [CrossRef] [PubMed]
    [Google Scholar]
  7. Cui H. , Yan Y. , Wei J. , Huang X. , Huang Y. , Ouyang Z. , Qin Q. . ( 2011b; ). Identification and functional characterization of an interferon regulatory factor 7-like (IRF7-like) gene from orange-spotted grouper, Epinephelus coioides . . Dev Comp Immunol 35:, 672–684. [CrossRef] [PubMed]
    [Google Scholar]
  8. D’Costa S. M. , Yao H. , Bilimoria S. L. . ( 2001; ). Transcription and temporal cascade in Chilo iridescent virus infected cells. . Arch Virol 146:, 2165–2178. [CrossRef] [PubMed]
    [Google Scholar]
  9. Ensser A. , Fleckenstein B. . ( 1995; ). Alcelaphine herpesvirus type 1 has a semaphorin-like gene. . J Gen Virol 76:, 1063–1067. [CrossRef] [PubMed]
    [Google Scholar]
  10. Fan J. , Mansfield S. G. , Redmond T. , Gordon-Weeks P. R. , Raper J. A. . ( 1993; ). The organization of F-actin and microtubules in growth cones exposed to a brain-derived collapsing factor. . J Cell Biol 121:, 867–878. [CrossRef] [PubMed]
    [Google Scholar]
  11. Finlay B. B. , McFadden G. . ( 2006; ). Anti-immunology: evasion of the host immune system by bacterial and viral pathogens. . Cell 124:, 767–782. [CrossRef] [PubMed]
    [Google Scholar]
  12. Gardner J. D. , Tscharke D. C. , Reading P. C. , Smith G. L. . ( 2001; ). Vaccinia virus semaphorin A39R is a 50-55 kDa secreted glycoprotein that affects the outcome of infection in a murine intradermal model. . J Gen Virol 82:, 2083–2093.[PubMed]
    [Google Scholar]
  13. Gong J. , Huang Y. H. , Huang X. H. , Zhang R. , Qin Q. W. . ( 2010; ). Nuclear-export-signal-dependent protein translocation of dUTPase encoded by Singapore grouper iridovirus. . Arch Virol 155:, 1069–1076. [CrossRef] [PubMed]
    [Google Scholar]
  14. Goshima Y. , Ito T. , Sasaki Y. , Nakamura F. . ( 2002; ). Semaphorins as signals for cell repulsion and invasion. . J Clin Invest 109:, 993–998. [CrossRef] [PubMed]
    [Google Scholar]
  15. Gravell M. , Malsberger R. G. . ( 1965; ). A permanent cell line from the fathead minnow (Pimephales promelas). . Ann N Y Acad Sci 126:, 555–565. [CrossRef] [PubMed]
    [Google Scholar]
  16. Holzerlandt R. , Orengo C. , Kellam P. , Albà M. M. . ( 2002; ). Identification of new herpesvirus gene homologs in the human genome. . Genome Res 12:, 1739–1748. [CrossRef] [PubMed]
    [Google Scholar]
  17. Huang X. H. , Huang Y. H. , Sun J. J. , Han X. , Qin Q. W. . ( 2009; ). Characterization of two grouper Epinephelus akaara cell lines: application to studies of Singapore grouper iridovirus (SGIV) propagation and virus-host interaction. . Aquaculture 292:, 172–179. [CrossRef]
    [Google Scholar]
  18. Huang Y. , Huang X. , Yan Y. , Cai J. , Ouyang Z. , Cui H. , Wang P. , Qin Q. . ( 2011; ). Transcriptome analysis of orange-spotted grouper (Epinephelus coioides) spleen in response to Singapore grouper iridovirus. . BMC Genomics 12:, 556. [CrossRef] [PubMed]
    [Google Scholar]
  19. Jia K. T. , Liu Z. Y. , Guo C. J. , Xia Q. , Mi S. , Li X. D. , Weng S. P. , He J. G. . ( 2013; ). The potential role of microfilaments in host cells for infection with infectious spleen and kidney necrosis virus infection. . Virol J 10:, 77. [CrossRef] [PubMed]
    [Google Scholar]
  20. Kalil K. , Dent E. W. . ( 2004; ). Hot +TIPS: guidance cues signal directly to microtubules. . Neuron 42:, 877–879. [CrossRef] [PubMed]
    [Google Scholar]
  21. Kallewaard N. L. , Bowen A. L. , Crowe J. E. Jr . ( 2005; ). Cooperativity of actin and microtubule elements during replication of respiratory syncytial virus. . Virology 331:, 73–81. [CrossRef] [PubMed]
    [Google Scholar]
  22. Kikuchi K. , Chédotal A. , Hanafusa H. , Ujimasa Y. , de Castro F. , Goodman C. S. , Kimura T. . ( 1999; ). Cloning and characterization of a novel class VI semaphorin, semaphorin Y. . Mol Cell Neurosci 13:, 9–23. [CrossRef] [PubMed]
    [Google Scholar]
  23. Kolodkin A. L. , Matthes D. J. , Goodman C. S. . ( 1993; ). The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules. . Cell 75:, 1389–1399. [CrossRef] [PubMed]
    [Google Scholar]
  24. Kumanogoh A. , Kikutani H. . ( 2003a; ). Immune semaphorins: a new area of semaphorin research. . J Cell Sci 116:, 3463–3470. [CrossRef] [PubMed]
    [Google Scholar]
  25. Kumanogoh A. , Kikutani H. . ( 2003b; ). Roles of the semaphorin family in immune regulation. . Adv Immunol 81:, 173–198. [CrossRef] [PubMed]
    [Google Scholar]
  26. Luo Y. , Weng S. , Wang Q. , Shi X. , Dong C. , Lu Q. , Yu X. , He J. . ( 2009; ). Tiger frog virus can infect zebrafish cells for studying up- or down-regulated genes by proteomics approach. . Virus Res 144:, 171–179. [CrossRef] [PubMed]
    [Google Scholar]
  27. Mahalingam S. , Meanger J. , Foster P. S. , Lidbury B. A. . ( 2002; ). The viral manipulation of the host cellular and immune environments to enhance propagation and survival: a focus on RNA viruses. . J Leukoc Biol 72:, 429–439.[PubMed]
    [Google Scholar]
  28. Murti K. G. , Goorha R. . ( 1983; ). Interaction of frog virus-3 with the cytoskeleton. I. Altered organization of microtubules, intermediate filaments, and microfilaments. . J Cell Biol 96:, 1248–1257. [CrossRef] [PubMed]
    [Google Scholar]
  29. Nakamura F. , Kalb R. G. , Strittmatter S. M. . ( 2000; ). Molecular basis of semaphorin-mediated axon guidance. . J Neurobiol 44:, 219–229. [CrossRef] [PubMed]
    [Google Scholar]
  30. Pasterkamp R. J. , Kolodkin A. L. . ( 2003; ). Semaphorin junction: making tracks toward neural connectivity. . Curr Opin Neurobiol 13:, 79–89. [CrossRef] [PubMed]
    [Google Scholar]
  31. Polster B. M. , Pevsner J. , Hardwick J. M. . ( 2004; ). Viral Bcl-2 homologs and their role in virus replication and associated diseases. . Biochim Biophys Acta 1644:, 211–227. [CrossRef] [PubMed]
    [Google Scholar]
  32. Qin Q. W. , Lam T. J. , Sin Y. M. , Shen H. , Chang S. F. , Ngoh G. H. , Chen C. L. . ( 2001; ). Electron microscopic observations of a marine fish iridovirus isolated from brown-spotted grouper, Epinephelus tauvina . . J Virol Methods 98:, 17–24. [CrossRef] [PubMed]
    [Google Scholar]
  33. Qin Q. W. , Chang S. F. , Ngoh-Lim G. H. , Gibson-Kueh S. , Shi C. , Lam T. J. . ( 2003; ). Characterization of a novel ranavirus isolated from grouper Epinephelus tauvina . . Dis Aquat Organ 53:, 1–9. [CrossRef] [PubMed]
    [Google Scholar]
  34. Qu X. , Wei H. , Zhai Y. , Que H. , Chen Q. , Tang F. , Wu Y. , Xing G. , Zhu Y. . & other authors ( 2002; ). Identification, characterization, and functional study of the two novel human members of the semaphorin gene family. . J Biol Chem 277:, 35574–35585. [CrossRef] [PubMed]
    [Google Scholar]
  35. Reed L. J. , Muench H. . ( 1938; ). A simple method of estimating fifty per cent endpoints. . Am J Epidemiol 27:, 493–497.
    [Google Scholar]
  36. Slobedman B. , Barry P. A. , Spencer J. V. , Avdic S. , Abendroth A. . ( 2009; ). Virus-encoded homologs of cellular interleukin-10 and their control of host immune function. . J Virol 83:, 9618–9629. [CrossRef] [PubMed]
    [Google Scholar]
  37. Song W. J. , Qin Q. W. , Qiu J. , Huang C. H. , Wang F. , Hew C. L. . ( 2004; ). Functional genomics analysis of Singapore grouper iridovirus: complete sequence determination and proteomic analysis. . J Virol 78:, 12576–12590. [CrossRef] [PubMed]
    [Google Scholar]
  38. Spriggs M. K. . ( 1996; ). One step ahead of the game: viral immunomodulatory molecules. . Annu Rev Immunol 14:, 101–130. [CrossRef] [PubMed]
    [Google Scholar]
  39. Spriggs M. K. . ( 1999; ). Shared resources between the neural and immune systems: semaphorins join the ranks. . Curr Opin Immunol 11:, 387–391. [CrossRef] [PubMed]
    [Google Scholar]
  40. Sultana H. , Neelakanta G. , Foellmer H. G. , Montgomery R. R. , Anderson J. F. , Koski R. A. , Medzhitov R. M. , Fikrig E. . ( 2012; ). Semaphorin 7A contributes to West Nile virus pathogenesis through TGF-β1/Smad6 signaling. . J Immunol 189:, 3150–3158. [CrossRef] [PubMed]
    [Google Scholar]
  41. Takamatsu H. , Okuno T. , Kumanogoh A. . ( 2010; ). Regulation of immune cell responses by semaphorins and their receptors. . Cell Mol Immunol 7:, 83–88. [CrossRef] [PubMed]
    [Google Scholar]
  42. Tamagnone L. , Comoglio P. M. . ( 2004; ). To move or not to move. ? EMBO Rep 5:, 356–361. [CrossRef] [PubMed]
    [Google Scholar]
  43. Taylor M. P. , Koyuncu O. O. , Enquist L. W. . ( 2011; ). Subversion of the actin cytoskeleton during viral infection. . Nat Rev Microbiol 9:, 427–439. [CrossRef] [PubMed]
    [Google Scholar]
  44. Teng Y. , Hou Z. , Gong J. , Liu H. , Xie X. , Zhang L. , Chen X. , Qin Q. W. . ( 2008; ). Whole-genome transcriptional profiles of a novel marine fish iridovirus, Singapore grouper iridovirus (SGIV) in virus-infected grouper spleen cell cultures and in orange-spotted grouper, Epinephulus coioides . . Virology 377:, 39–48. [CrossRef] [PubMed]
    [Google Scholar]
  45. Tortorella D. , Gewurz B. E. , Furman M. H. , Schust D. J. , Ploegh H. L. . ( 2000; ). Viral subversion of the immune system. . Annu Rev Immunol 18:, 861–926. [CrossRef] [PubMed]
    [Google Scholar]
  46. Tran T. S. , Kolodkin A. L. , Bharadwaj R. . ( 2007; ). Semaphorin regulation of cellular morphology. . Annu Rev Cell Dev Biol 23:, 263–292. [CrossRef] [PubMed]
    [Google Scholar]
  47. Tsai C. T. , Ting J. W. , Wu M. H. , Wu M. F. , Guo I. C. , Chang C. Y. . ( 2005; ). Complete genome sequence of the grouper iridovirus and comparison of genomic organization with those of other iridoviruses. . J Virol 79:, 2010–2023. [CrossRef] [PubMed]
    [Google Scholar]
  48. Walzer T. , Galibert L. , Comeau M. R. , De Smedt T. . ( 2005; ). Plexin C1 engagement on mouse dendritic cells by viral semaphorin A39R induces actin cytoskeleton rearrangement and inhibits integrin-mediated adhesion and chemokine-induced migration. . J Immunol 174:, 51–59.[PubMed] [CrossRef]
    [Google Scholar]
  49. Xia L. , Cao J. , Huang X. , Qin Q. . ( 2009; ). Characterization of Singapore grouper iridovirus (SGIV) ORF086R, a putative homolog of ICP18 involved in cell growth control and virus replication. . Arch Virol 154:, 1409–1416. [CrossRef] [PubMed]
    [Google Scholar]
  50. Xu X. M. , Fisher D. A. , Zhou L. , White F. A. , Ng S. , Snider W. D. , Luo Y. . ( 2000; ). The transmembrane protein semaphorin 6A repels embryonic sympathetic axons. . J Neurosci 20:, 2638–2648.[PubMed]
    [Google Scholar]
  51. Xu D. , Wei J. , Cui H. , Gong J. , Yan Y. , Lai R. , Qin Q. . ( 2010; ). Differential profiles of gene expression in grouper Epinephelus coioides, infected with Singapore grouper iridovirus, revealed by suppression subtractive hybridization and DNA microarray. . J Fish Biol 77:, 341–360. [CrossRef] [PubMed]
    [Google Scholar]
  52. Yan Y. , Cui H. , Guo C. , Li J. , Huang X. , Wei J. , Qin Q. . ( 2013; ). An insulin-like growth factor homologue of Singapore grouper iridovirus modulates cell proliferation, apoptosis and enhances viral replication. . J Gen Virol 94:, 2759–2770. [CrossRef] [PubMed]
    [Google Scholar]
  53. Yazdani U. , Terman J. R. . ( 2006; ). The semaphorins. . Genome Biol 7:, 211. [CrossRef] [PubMed]
    [Google Scholar]
  54. Zhou Y. , Gunput R. A. F. , Pasterkamp R. J. . ( 2008; ). Semaphorin signaling: progress made and promises ahead. . Trends Biochem Sci 33:, 161–170. [CrossRef] [PubMed]
    [Google Scholar]
  55. Zhou J. G. , Wei J. G. , Xu D. , Cui H. C. , Yan Y. , Ou-Yang Z. L. , Huang X. H. , Huang Y. H. , Qin Q. W. . ( 2011; ). Molecular cloning and characterization of two novel hepcidins from orange-spotted grouper, Epinephelus coioides . . Fish Shellfish Immunol 30:, 559–568. [CrossRef] [PubMed]
    [Google Scholar]
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