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
2021-01-19
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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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