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Induction of Epstein-Barr virus (EBV) lytic cycle in vitro causes oxidative stress in lymphoblastoid B cell lines

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Abstract

Here, we investigated the effect of induction of the Epstein-Barr virus (EBV) viral lytic cycle on the oxidant/antioxidant balance in three lymphoblastoid cell lines: B95-8, Raji, and LCL C1. The induction of the EBV lytic cycle was done by a non-stressing dose of 12-0-tetradecanoylphorbol-13-acetate (8 nM). Oxidative stress was assessed by measuring malondialdehyde as a parameter of lipid peroxidation, the levels of glutathione, and the activities of three antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase). After 48 h (peak of lytic cycle), a significant decrease in superoxide dismutase activity was observed in B95-8, Raji, and LCL C1 cells (P < 0.05). In addition, in B95-8 cells also a significant decrease of catalase activity was detected (P < 0.05). The glutathione peroxidase activity and the glutathione level were not significantly modified by the induction in any of the cell lines. We found a significant rise in malondialdehyde levels in B95-8, Raji, and LCL C1 cells after the induction of the lytic cycle compared to controls (P < 0.05). In conclusion, induction of EBV lytic cycle in lymphoblastoid cells causes increased oxidative stress in the host cells within 48 h, a process that could be involved in malignant transformations.

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References

  1. Babkock JG, Decker LL, Volk M et al (1998) EBV persistence in memory B cells in vivo. Immunity 3:395–404. doi:10.1016/S1074-7613(00)80622-6

    Article  Google Scholar 

  2. Tierney RJ, Steven N, Young LS et al (1994) Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. J Virol 68:7374–7385

    PubMed  CAS  Google Scholar 

  3. Anagnostopoulus I, Hummel M, Kreschel C et al (1995) Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus. Blood 3:744–750

    Google Scholar 

  4. Sixbey JW, Nedrud JG, Raab-Traub N et al (1984) Epstein-Barr virus replication in oropharyngeal epithelial cells. N Engl J Med 19:1225–1230

    Article  Google Scholar 

  5. Crawford DH (2001) Biology and disease associations of Epstein-Barr virus. Philos Trans R Soc Lond B Biol Sci 356:461–473. doi:10.1098/rstb.2000.0783

    Article  PubMed  CAS  Google Scholar 

  6. Speck SH, Chatila T, Flemington E (1997) Reactivation of Epstein-Barr virus: regulation and function of the BZLF1 gene. Trends Microbiol 5:399–405. doi:10.1016/S0966-842X(97)01129-3

    Article  PubMed  CAS  Google Scholar 

  7. Zur Hausen H, O’Neil F, Freese U (1978) Persisting oncogenic herpes viruses induced by the tumor promoter TPA. Nature 272:373–375. doi:10.1038/272373a0

    Article  PubMed  CAS  Google Scholar 

  8. Hampar B, Derge JG, Martos LM et al (1973) Identification of a critical period during the S phase for activation of the Epstein-Barr virus by 5-iododeoxyuridine. Nat New Biol 244:214–217

    CAS  Google Scholar 

  9. Luka J, Kallin B, Klein G (1979) Induction of the Epstein-Barr virus (EBV) cycle in latently infected cells by n-butyrate. Virology 94:228–231. doi:10.1016/0042-6822(79)90455-0

    Article  PubMed  CAS  Google Scholar 

  10. Faggioni A, Zompetta C, Grimaldi S et al (1986) Calcium modulation activates Epstein-Barr virus genome in latently infected cells. Science 232:1554–1556. doi:10.1126/science.3012779

    Article  PubMed  CAS  Google Scholar 

  11. Fahmi H, Cochet C, Hmama Z et al (2000) Transforming growth factor beta 1 stimulates expression of the Epstein-Barr virus BZLF1 immediate-early gene product ZEBRA by an indirect mechanism which requires the MAPK kinase pathway. J Virol 74:5810–5818. doi:10.1128/JVI.74.13.5810-5818.2000

    Article  PubMed  CAS  Google Scholar 

  12. Takada K (1984) Cross-linking of cell surface immunoglobulins induces Epstein-Barr virus in Burkitt lymphoma lines. Int J Cancer 33:27–32. doi:10.1002/ijc.2910330106

    Article  PubMed  CAS  Google Scholar 

  13. Brady G, Mac Arthur GJ, Fanel PJ (2007) Epstein-Barr virus and Burkitt lymphoma. J Clin Pathol 60:1397–1402

    PubMed  CAS  Google Scholar 

  14. Raab-traub N (1992) Epstein-Barr virus and nasopharyngeal carcinoma. Semin Cancer Biol 3:297–307

    PubMed  CAS  Google Scholar 

  15. Takada K (1999) Epstein-Barr virus and gastric carcinoma. EBV Rep 6:95–100

    Google Scholar 

  16. Humme S, Reisbach G, Feederle R et al (2003) The EBV nuclear antigen 1 (EBNA1) enhances B cell immortalization several thousandfold. Proc Natl Acad Sci USA 100:10989–10994. doi:10.1073/pnas.1832776100

    Article  PubMed  CAS  Google Scholar 

  17. Kitagawa N, Goto M, Kurozumi K et al (2000) Epstein-Barr virus-encoded poly (A) RNA supports Burkitt’s lymphoma growth through interleukin-10 induction. EMBO J 19:6742–6750. doi:10.1093/emboj/19.24.6742

    Article  PubMed  CAS  Google Scholar 

  18. Tomkinson B, Robertson E, Kieff E (1993) Epstein-Barr virus nuclear proteins EBNA-3A and EBNA-3C are essential for B-lymphocyte growth transformation. J Virol 67:2014–2025

    PubMed  CAS  Google Scholar 

  19. Jones TG, Wood JD (1996) Oxidant production by human B lymphocytes: detection of activity and identification of components involved. Methods 9:619–627. doi:10.1006/meth.1996.0068

    Article  PubMed  CAS  Google Scholar 

  20. Cerimele F, Battle T, Lynch R et al (2005) Reactive oxygen signaling and MAPK activation distinguish Epstein-Barr virus (EBV)-positive versus EBV-negative Burkitt’s lymphoma. Proc Natl Acad Sci USA 102:175–179. doi:10.1073/pnas.0408381102

    Article  PubMed  CAS  Google Scholar 

  21. Dalpke AH, Thomssen R, Ritter K (2003) Oxidative injury to endothelial cells due to Epstein-Barr virus-induced autoantibodies against manganese superoxide dismutase. J Med Virol 3:408–416. doi:10.1002/jmv.10501

    Article  CAS  Google Scholar 

  22. Valko M, Leibfritz D, Moncol J et al (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84. doi:10.1016/j.biocel.2006.07.001

    Article  PubMed  CAS  Google Scholar 

  23. Valko M, Rhodes CJ, Moncol J et al (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40. doi:10.1016/j.cbi.2005.12.009

    Article  PubMed  CAS  Google Scholar 

  24. Kovacic P, Jacintho JD (2001) Mechanisms of carcinogenesis. Focus on oxidative stress and electron transfer. Curr Med Chem 8:773–796

    PubMed  CAS  Google Scholar 

  25. Ridnour LA, Isenberg JS, Espey MG et al (2005) Nitric oxide regulates angiogenesis through a functional switch involving thrombospondin-1. Proc Natl Acad Sci USA 102:13152–13747. doi:10.1073/pnas.0502979102

    Article  CAS  Google Scholar 

  26. Valko M, Morris H, Mazur M et al (2001) Oxygen free radical generating mechanisms in the colon: Do the semiquinones of vitamin K play a role in the aetiology of colon cancer? Biochim Biophys Acta 1527:161–166

    PubMed  CAS  Google Scholar 

  27. Ames BN (1983) Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative disease. Science 221:1256–1264. doi:10.1126/science.6351251

    Article  PubMed  CAS  Google Scholar 

  28. Fridovich I (1978) The biology of oxygen radicals. Science 201:875–880. doi:10.1126/science.210504

    Article  PubMed  CAS  Google Scholar 

  29. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  PubMed  CAS  Google Scholar 

  30. Yung-Chi C (1980) Studies on the activity of DNase associated with the replication of the Epstein-Barr virus. Virology 100:334–338

    Article  Google Scholar 

  31. Kieff E (1996) Epstein-Barr virus and its replication. In: Field BN, Knipe NM, Howley PM et al (eds) Fields virology, 3rd edn. Lippincott-Raven Publishers, Philadelphia

    Google Scholar 

  32. Miller G, Lipman M (1973) Release of infectious Epstein-Barr virus by transformed marmoset leukocytes. Proc Natl Acad Sci USA 70:190–194

    Article  PubMed  CAS  Google Scholar 

  33. Oh HM, Oh JM, Choi SC et al (2003) An efficient method for the rapid establishment of Epstein-Barr virus immortalization of human B lymphocytes. Cell Prolif 36:191–197

    Article  PubMed  Google Scholar 

  34. Fachiroh J, Schouten T, Hariwiyanto B et al (2004) Molecular diversity of Epstein-Barr virus IgG and IgA antibody responses in nasopharyngeal carcinoma: a comparison on Indonesian, Chinese, and European subjects. J Infect Dis 190:53–62

    Article  PubMed  CAS  Google Scholar 

  35. Akerboom TPM, Sies H (1981) Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples. Methods Enzymol 77:373–382

    Article  PubMed  CAS  Google Scholar 

  36. Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 3:469–474

    Article  Google Scholar 

  37. Steghens JP, Van Kappel AL, Denis I et al (2001) Diaminophthalene, a new highly specific reagent for HPLC-UV measurement of total and free malondialdehyde in human plasma or serum. Free Radic Biol Med 31:242–249

    Article  PubMed  CAS  Google Scholar 

  38. Lassoued S, Ben Ameur R, Ayadi W et al (2008) Epstein-Barr virus induces an oxidative stress during the early stages of infection in B lymphocytes, epithelial, and lymphoblastoid cell lines. Mol Cell Biochem 313:179–186

    Article  PubMed  CAS  Google Scholar 

  39. Zhang M, Liu L, Cheng L et al (2003) Express of plasma ROS, SOD and GSH-PX in patients with nasopharyngeal carcinoma. Lin Chuang Er Bi Yan Hou Ke Za Zhi 11:650–651

    Google Scholar 

  40. Montone KT, Hodinka RL, Salhany KE et al (1996) Identification of Epstein-Barr virus lytic activity in post-transplantation lymphoproliferative disease. Mod Pathol 9:621–630

    PubMed  CAS  Google Scholar 

  41. Tao Q, Robertson KD, Manns A et al (1998) Epstein-Barr virus (EBV) in endemic Burkitt’s lymphoma: molecular analysis of primary tumor tissue. Blood 91:1373–1381

    PubMed  CAS  Google Scholar 

  42. Hong GK, Gulley ML, Feng WH et al (2005) Epstein-Barr virus infection contributes to lymphoproliferative disease in SCID mose model. J Virol 79:13993–14003

    Article  PubMed  CAS  Google Scholar 

  43. Spieker T, Herbst H (2000) Distribution and phenotype of Epstein-Barr virus-infected cells in inflammatory bowel disease. Am J Pathol 1:51–57

    Google Scholar 

  44. Regöly-Merei A, Bereczky M, Arató G et al (2007) Nutritional and antioxidant status of colorectal cancer patients. Orv Hetil 148:1505–1509

    Article  PubMed  Google Scholar 

  45. Toussirot E, Roudier J (2007) Pathophysiological links between rheumatoid arthritis and the Epstein-Barr virus: An update. Joint Bone Spine 74:418–426

    Article  PubMed  CAS  Google Scholar 

  46. Sarban S, Kocyigit A, Yazar M et al (2005) Plasma total antioxidant capacity, lipid peroxidation, and erythrocyte antioxidant enzyme activities in patients with rheumatoid arthritis and osteoarthritis. Clin Biochem 38:981–986

    Article  PubMed  CAS  Google Scholar 

  47. Niedobitek G, Agathanggelou A, Herbst H et al (1997) Epstein-Barr virus (EBV) infection in infectious mononucleosis: virus latency, replication and phenotype of EBV-infected cells. J Pathol 182:151–159

    Article  PubMed  CAS  Google Scholar 

  48. Prang NS, Hornef MW, Jäger M et al (1997) Lytic replication of Epstein-Barr virus in the peripheral blood: analysis of viral gene expression in B lymphocytes during infectious mononucleosis and in the normal carrier state. Blood 89:1665–1677

    PubMed  CAS  Google Scholar 

  49. Qadri I, Iwahashi M, Capasso JM et al (2004) Induced oxidative stress and activated expression of manganese superoxide dismutase during hepatitis C virus replication: role of JNK, p38 MAPK and AP-1. Biochem J 378:919–928

    Article  PubMed  CAS  Google Scholar 

  50. Severi T, Ying C, Vermeesch JR et al (2006) Hepatitis B virus replication causes oxidative stress in HepAD38 liver cells. Mol Cell Biochem 290:79–85

    Article  PubMed  CAS  Google Scholar 

  51. Dikalov S, Wei L, Mehrampour P et al (2007) Production of extracellular superoxide by human lymphoblast cell lines: comparison of electron spin resonance techniques and cytochrome C reduction assay. Biochem Pharmacol 9290:1–9

    Google Scholar 

  52. Dröge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95

    PubMed  Google Scholar 

  53. Abdalla MY, Ahmad IM, Spitz DR et al (2005) Hepatitis C virus-core and non structural proteins lead to different effects on cellular antioxidant defenses. J Med Virol 76:489–497

    Article  PubMed  CAS  Google Scholar 

  54. Biggin M, Bodescot M, Perricaudet M et al (1987) Epstein-Barr virus gene expression in P3HR1-superinfected Raji cells. J Virol 61:3120–3132

    PubMed  CAS  Google Scholar 

  55. De Turenne-Tessier M, Ooka T, De The G et al (1986) Characterization of an Epstein-Barr virus-induced thymidine kinase. J Virol 57:1105–1112

    PubMed  Google Scholar 

  56. Ooka T, Calender A, de Turenne M et al (1983) Effect of arabinofuranosylthymine on the replication of Epstein-Barr virus and relationship with a new induced thymidine kinase activity. J Virol 46:187–195

    PubMed  CAS  Google Scholar 

  57. Ooka T, Lenoir G, Decaussin G et al (1986) Epstein-Barr virus-specific DNA polymerase in virus-nonproducer Raji cells. J Virol 58:671–675

    PubMed  CAS  Google Scholar 

  58. LaJeunesse DR, Brooks K, Adamson AL (2005) Epstein–Barr virus immediate-early proteins BZLF1 and BRLF1 alter mitochondrial morphology during lytic replication. Biochem Biophys Res Commun 333:438–442

    Article  PubMed  CAS  Google Scholar 

  59. Korenaga M, Wang T, Li Y et al (2005) Hepatitis C virus core protein inhibits mitochondrial electron transport and increases reactive oxygen species (ROS) production. J Biol Chem 280:37481–37488

    Article  PubMed  CAS  Google Scholar 

  60. Bureau C, Bernard J, Chaouche N et al (2001) Nonstructural 3 protein of hepatitis C virus triggers an oxidative burst in human monocytes via activation of NADPH oxidase. J Biol Chem 276:23077–23083

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

We want to acknowledge the excellent technical assistance of Mrs. Petra Windmolders and Mr. Marcel Zeegers.

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Authors and Affiliations

  1. Unité de Biotechnologie et Pathologies, Institut Supérieur de Biotechnologie de Sfax, Sfax, Tunisia

    Bochra Gargouri, Hammadi Attia & Saloua Lassoued

  2. BP 31 Sidi Abbes, 3062, Sfax, Tunisia

    Bochra Gargouri

  3. Department of Hepatology, University Hospital Gasthuisberg, Louvain, Belgium

    Jos Van Pelt

  4. Unité de Physiologie Animale, Faculté des Sciences de Sfax, Sfax, Tunisia

    Abd El Fatteh El Feki

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  1. Bochra Gargouri
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  2. Jos Van Pelt
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  3. Abd El Fatteh El Feki
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  4. Hammadi Attia
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  5. Saloua Lassoued
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Correspondence to Bochra Gargouri.

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Gargouri, B., Van Pelt, J., El Feki, A.E.F. et al. Induction of Epstein-Barr virus (EBV) lytic cycle in vitro causes oxidative stress in lymphoblastoid B cell lines. Mol Cell Biochem 324, 55–63 (2009). https://doi.org/10.1007/s11010-008-9984-1

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