1887

Abstract

Insulin-like growth factors (IGFs) play crucial roles in regulating cell differentiation, proliferation and apoptosis. In this study, a novel IGF homologue gene (IGF-like) encoded by Singapore grouper iridovirus (SGIV) ORF062R (termed ), was cloned and characterized. The coding region of is 771 bp in length, with a variable number of tandem repeats (VNTR) locus at the 3′-end. We cloned one isoform of this novel gene, 582 bp in length, containing the predicted IGF domain and 3.6 copy numbers of the 27 bp repeat unit. was an early transcribed gene during viral infection, and SGIV–IGF was distributed predominantly in the cytoplasm with a diffused granular appearance. Intriguingly, overexpression of SGIV–IGF was able to promote the growth of grouper embryonic cells (GP cells) by promoting G1/S phase transition, which was at least partially dependent on its 3′-end VNTR locus. Furthermore, viral titre assay and real-time quantitative PCR (RT-qPCR) analysis proved that SGIV–IGF could promote SGIV replication in grouper cells. In addition, overexpression of SGIV–IGF mildly facilitated apoptosis in SGIV-infected non-host fathead minnow (FHM) cells. Together, our study demonstrated a novel functional gene of SGIV which may regulate viral replication and cellular processes through multiple mechanisms that appear to be cell type-dependent.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.056135-0
2013-12-01
2019-11-21
Loading full text...

Full text loading...

/deliver/fulltext/jgv/94/12/2759.html?itemId=/content/journal/jgv/10.1099/vir.0.056135-0&mimeType=html&fmt=ahah

References

  1. Baker J. , Liu J. P. , Robertson E. J. , Efstratiadis A. . ( 1993; ). Role of insulin-like growth factors in embryonic and postnatal growth. . Cell 75:, 73–82.[PubMed] [CrossRef]
    [Google Scholar]
  2. Beck K. D. , Powell-Braxton L. , Widmer H. R. , Valverde J. , Hefti F. . ( 1995; ). Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons. . Neuron 14:, 717–730. [CrossRef] [PubMed]
    [Google Scholar]
  3. Brisken C. , Ayyannan A. , Nguyen C. , Heineman A. , Reinhardt F. , Tan J. , Dey S. K. , Dotto G. P. , Weinberg R. A. . ( 2002; ). IGF-2 is a mediator of prolactin-induced morphogenesis in the breast. . Dev Cell 3:, 877–887. [CrossRef] [PubMed]
    [Google Scholar]
  4. Cheng C. M. , Joncas G. , Reinhardt R. R. , Farrer R. , Quarles R. , Janssen J. , McDonald M. P. , Crawley J. N. , Powell-Braxton L. , Bondy C. A. . ( 1998; ). Biochemical and morphometric analyses show that myelination in the insulin-like growth factor 1 null brain is proportionate to its neuronal composition. . J Neurosci 18:, 5673–5681.[PubMed]
    [Google Scholar]
  5. Chinchar V. G. . ( 2002; ). Ranaviruses (family Iridoviridae): emerging cold-blooded killers. . Arch Virol 147:, 447–470. [CrossRef] [PubMed]
    [Google Scholar]
  6. Cohick W. S. , Clemmons D. R. . ( 1993; ). The insulin-like growth factors. . Annu Rev Physiol 55:, 131–153. [CrossRef] [PubMed]
    [Google Scholar]
  7. Cui H. C. , Yan Y. , Wei J. G. , Hou Z. W. , Huang Y. H. , Huang X. H. , Qin Q. W. . ( 2011; ). Cloning, characterization, and expression analysis of orange-spotted grouper (Epinephelus coioides) ILF2 gene (EcILF2). . Fish Shellfish Immunol 30:, 378–388. [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. de Koning A. P. J. , Gu W. J. , Castoe T. A. , Batzer M. A. , Pollock D. D. . ( 2011; ). Repetitive elements may comprise over two-thirds of the human genome. . PLoS Genet 7:, e1002384. [CrossRef] [PubMed]
    [Google Scholar]
  10. DeChiara T. M. , Efstratiadis A. , Robertson E. J. . ( 1990; ). A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. . Nature 345:, 78–80. [CrossRef] [PubMed]
    [Google Scholar]
  11. Duguay S. J. , Jin Y. , Stein J. , Duguay A. N. , Gardner P. , Steiner D. F. . ( 1998; ). Post-translational processing of the insulin-like growth factor-2 precursor. Analysis of O-glycosylation and endoproteolysis. . J Biol Chem 273:, 18443–18451. [CrossRef] [PubMed]
    [Google Scholar]
  12. Dupont J. , Karas M. , LeRoith D. . ( 2000; ). The potentiation of estrogen on insulin-like growth factor I action in MCF-7 human breast cancer cells includes cell cycle components. . J Biol Chem 275:, 35893–35901. [CrossRef] [PubMed]
    [Google Scholar]
  13. Dupont J. , Pierre A. , Froment P. , Moreau C. . ( 2003; ). The insulin-like growth factor axis in cell cycle progression. . Horm Metab Res 35:, 740–750. [CrossRef] [PubMed]
    [Google Scholar]
  14. Emmett S. R. Sr , Dove B. , Mahoney L. , Wurm T. , Hiscox J. A. . ( 2005; ). The cell cycle and virus infection. . Methods Mol Biol 296:, 197–218.[PubMed]
    [Google Scholar]
  15. Fernández M. C. , Venara M. , Nowicki S. , Chemes H. E. , Barontini M. , Pennisi P. A. . ( 2012; ). Igf-I regulates pheochromocytoma cell proliferation and survival in vitro and in vivo. . Endocrinology 153:, 3724–3734. [CrossRef] [PubMed]
    [Google Scholar]
  16. Fuke S. , Suo S. , Takahashi N. , Koike H. , Sasagawa N. , Ishiura S. . ( 2001; ). The VNTR polymorphism of the human dopamine transporter (DAT1) gene affects gene expression. . Pharmacogenomics J 1:, 152–156. [CrossRef] [PubMed]
    [Google Scholar]
  17. 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]
  18. Gooch J. L. , Van Den Berg C. L. , Yee D. . ( 1999; ). Insulin-like growth factor (IGF)-I rescues breast cancer cells from chemotherapy-induced cell death–proliferative and anti-apoptotic effects. . Breast Cancer Res Treat 56:, 1–10. [CrossRef] [PubMed]
    [Google Scholar]
  19. 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]
  20. Guo Q. W. , Qian L. , Guo L. , Shi M. , Chen C. G. , Lv X. , Yu M. , Hu M. R. , Jiang G. S. , Guo N. . ( 2010; ). Transactivators Zta and Rta of Epstein–Barr virus promote G0/G1 to S transition in Raji cells: a novel relationship between lytic virus and cell cycle. . Mol Immunol 47:, 1783–1792. [CrossRef] [PubMed]
    [Google Scholar]
  21. Hamelers I. H. L. , van Schaik R. F. M. A. , Sipkema J. , Sussenbach J. S. , Steenbergh P. H. . ( 2002; ). Insulin-like growth factor I triggers nuclear accumulation of cyclin D1 in MCF-7S breast cancer cells. . J Biol Chem 277:, 47645–47652. [CrossRef] [PubMed]
    [Google Scholar]
  22. Hardy K. J. , Ussery D. W. , Oppenheim B. A. , Hawkey P. M. . ( 2004; ). Distribution and characterization of staphylococcal interspersed repeat units (SIRUs) and potential use for strain differentiation. . Microbiology 150:, 4045–4052. [CrossRef] [PubMed]
    [Google Scholar]
  23. Hellawell G. O. , Turner G. D. H. , Davies D. R. , Poulsom R. , Brewster S. F. , Macaulay V. M. . ( 2002; ). Expression of the type 1 insulin-like growth factor receptor is up-regulated in primary prostate cancer and commonly persists in metastatic disease. . Cancer Res 62:, 2942–2950.[PubMed]
    [Google Scholar]
  24. Hills F. A. , Mehmet H. , Sullivan M. H. . ( 2012; ). Insulin-like growth factor-II and heparin are anti-apoptotic survival factors in human villous cytotrophoblast. . Eur J Obstet Gynecol Reprod Biol 163:, 11–16. [CrossRef] [PubMed]
    [Google Scholar]
  25. Hoa T. T. T. , Zwart M. P. , Phuong N. T. , de Jong M. C. M. , Vlak J. M. . ( 2012; ). Low numbers of repeat units in variable number of tandem repeats (VNTR) regions of white spot syndrome virus are correlated with disease outbreaks. . J Fish Dis 35:, 817–826.[PubMed]
    [Google Scholar]
  26. Holly J. M. P. , Gunnell D. J. , Davey Smith G. . ( 1999; ). Growth hormone, IGF-I and cancer. Less intervention to avoid cancer? More intervention to prevent cancer?. J Endocrinol 162:, 321–330. [CrossRef] [PubMed]
    [Google Scholar]
  27. 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]
  28. Huang X. H. , Huang Y. H. , Ouyang Z. L. , Xu L. X. , Yan Y. , Cui H. C. , Han X. , Qin Q. W. . ( 2011; ). Singapore grouper iridovirus, a large DNA virus, induces nonapoptotic cell death by a cell type dependent fashion and evokes ERK signaling. . Apoptosis 16:, 831–845. [CrossRef] [PubMed]
    [Google Scholar]
  29. Iwanaga R. , Ozono E. , Fujisawa J. , Ikeda M. A. , Okamura N. , Huang Y. , Ohtani K. . ( 2008; ). Activation of the cyclin D2 and cdk6 genes through NF-kappaB is critical for cell-cycle progression induced by HTLV-I Tax. . Oncogene 27:, 5635–5642. [CrossRef] [PubMed]
    [Google Scholar]
  30. Jones J. I. , Clemmons D. R. . ( 1995; ). Insulin-like growth factors and their binding proteins: biological actions. . Endocr Rev 16:, 3–34.[PubMed]
    [Google Scholar]
  31. Kang B. P. , Urbonas A. , Baddoo A. , Baskin S. , Malhotra A. , Meggs L. G. . ( 2003; ). IGF-1 inhibits the mitochondrial apoptosis program in mesangial cells exposed to high glucose. . Am J Physiol Renal Physiol 285:, F1013–F1024.[PubMed] [CrossRef]
    [Google Scholar]
  32. Kawakami A. , Nakashima T. , Tsuboi M. , Urayama S. , Matsuoka N. , Ida H. , Kawabe Y. , Sakai H. , Migita K. . & other authors ( 1998; ). Insulin-like growth factor I stimulates proliferation and Fas-mediated apoptosis of human osteoblasts. . Biochem Biophys Res Commun 247:, 46–51. [CrossRef] [PubMed]
    [Google Scholar]
  33. Lai A. , Sarcevic B. , Prall O. W. J. , Sutherland R. L. . ( 2001; ). Insulin/insulin-like growth factor-I and estrogen cooperate to stimulate cyclin E-Cdk2 activation and cell cycle progression in MCF-7 breast cancer cells through differential regulation of cyclin E and p21(WAF1/Cip1). . J Biol Chem 276:, 25823–25833. [CrossRef] [PubMed]
    [Google Scholar]
  34. Laviola L. , Natalicchio A. , Giorgino F. . ( 2007; ). The IGF-I signaling pathway. . Curr Pharm Des 13:, 663–669. [CrossRef] [PubMed]
    [Google Scholar]
  35. Mairet-Coello G. , Tury A. , DiCicco-Bloom E. . ( 2009; ). Insulin-like growth factor-1 promotes G(1)/S cell cycle progression through bidirectional regulation of cyclins and cyclin-dependent kinase inhibitors via the phosphatidylinositol 3-kinase/Akt pathway in developing rat cerebral cortex. . J Neurosci 29:, 775–788. [CrossRef] [PubMed]
    [Google Scholar]
  36. Nascimento R. , Costa H. , Parkhouse R. M. E. . ( 2012; ). Virus manipulation of cell cycle. . Protoplasma 249:, 519–528. [CrossRef] [PubMed]
    [Google Scholar]
  37. Paquette J. , Giannoukakis N. , Polychronakos C. , Vafiadis P. , Deal C. . ( 1998; ). The INS 5′ variable number of tandem repeats is associated with IGF2 expression in humans. . J Biol Chem 273:, 14158–14164. [CrossRef] [PubMed]
    [Google Scholar]
  38. Planas J. V. , Mendez E. , Banos N. , Capilla E. , Castillo J. , Navarro I. , Gutierrez J. . ( 2000; ). Fish insulin, IGF-I and IGP-II receptors: a phylogenetic approach. . Am Zool 40:, 223–233. [CrossRef]
    [Google Scholar]
  39. Popken G. J. , Hodge R. D. , Ye P. , Zhang J. H. , Ng W. N. , O’Kusky J. R. , D’Ercole A. J. . ( 2004; ). In vivo effects of insulin-like growth factor-I (IGF-I) on prenatal and early postnatal development of the central nervous system. . Eur J Neurosci 19:, 2056–2068. [CrossRef] [PubMed]
    [Google Scholar]
  40. 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]
  41. 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]
  42. Raile K. , Hille R. , Laue S. , Schulz A. , Pfeifer G. , Horn F. , Kiess W. . ( 2003; ). Insulin-like growth factor I (IGF-I) stimulates proliferation but also increases caspase-3 activity, Annexin-V binding, and DNA-fragmentation in human MG63 osteosarcoma cells: co-activation of pro- and anti-apoptotic pathways by IGF-I. . Horm Metab Res 35:, 786–793. [CrossRef] [PubMed]
    [Google Scholar]
  43. Reed L. J. , Muench H. . ( 1938; ). A simple method of estimating 50% endpoints. . Am J Epidemiol 27:, 493–497. [CrossRef] [PubMed]
    [Google Scholar]
  44. Ren M. , Zhong X. , Ma C. Y. , Sun Y. , Guan Q. B. , Cui B. , Guo J. , Wang H. , Gao L. , Zhao J. J. . ( 2009; ). Insulin-like growth factor-1 promotes cell cycle progression via upregulation of cyclin D1 expression through the phosphatidylinositol 3-kinase/nuclear factor-kappaB signaling pathway in FRTL thyroid cells. . Acta Pharmacol Sin 30:, 113–119. [CrossRef] [PubMed]
    [Google Scholar]
  45. 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]
  46. Tamaki K. , Jeffreys A. J. . ( 2005; ). Human tandem repeat sequences in forensic DNA typing. . Leg Med (Tokyo) 7:, 244–250. [CrossRef] [PubMed]
    [Google Scholar]
  47. Teng Y. , Hou Z. W. , Gong J. , Liu H. , Xie X. Y. , Zhang L. , Chen X. H. , 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]
  48. 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]
  49. van der Burg B. , Isbrücker L. , van Selm-Miltenburg A. J. P. , de Laat S. W. , van Zoelen E. J. J. . ( 1990; ). Role of estrogen-induced insulin-like growth factors in the proliferation of human breast cancer cells. . Cancer Res 50:, 7770–7774.[PubMed]
    [Google Scholar]
  50. Xia L. Q. , Cao J. H. , Huang X. H. , Qin Q. W. . ( 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]
  51. Yang B. C. , Chang H. M. , Wang Y. S. , Chen R. F. , Lin S. J. . ( 1996; ). Transient induction of apoptosis in serum-starved glioma cells by insulin and IGF-1. . Biochim Biophys Acta 1314:, 83–92. [CrossRef] [PubMed]
    [Google Scholar]
  52. Yoon S. L. , Jung S. I. , Do E. J. , Lee S. R. , Lee S. Y. , Chu I. S. , Kim W. J. , Jung J. , Kim C. S. . & other authors ( 2010; ). Short rare hTERT-VNTR2-2nd alleles are associated with prostate cancer susceptibility and influence gene expression. . BMC Cancer 10:, 393. [CrossRef] [PubMed]
    [Google Scholar]
  53. Yu H. , Bauer B. , Lipke G. K. , Phillips R. L. , Van Zant G. . ( 1993; ). Apoptosis and hematopoiesis in murine fetal liver. . Blood 81:, 373–384.[PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.056135-0
Loading
/content/journal/jgv/10.1099/vir.0.056135-0
Loading

Data & Media loading...

Supplements

Supplementary material 

PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error