1887

Abstract

Chronic infections by the hepatotropic viruses hepatitis B virus (HBV) and hepatitis C virus (HCV) are major risk factors for the development of hepatocellular carcinoma (HCC). It is estimated that more than 700 000 individuals per year die from HCC, and around 80 % of HCC is attributable to HBV or HCV infection. Despite the clear clinical importance of virus-associated HCC, the underlying molecular mechanisms remain largely elusive. Oxidative stress, in particular DNA lesions associated with oxidative damage, play a major contributory role in carcinogenesis, and are strongly linked to the development of many cancers, including HCC. A large body of evidence demonstrates that both HBV and HCV induce hepatic oxidative stress, with increased oxidative DNA damage being observed both in infected individuals and in murine models of infection. Here, we review the impact of HBV and HCV on the incidence and repair of oxidative DNA damage. We begin by giving a brief overview of oxidative stress and the repair of DNA lesions induced by oxidative stress. We then review in detail the evidence surrounding the mechanisms by which both viruses stimulate oxidative stress, before focusing on how the viral proteins themselves may perturb the cellular response to oxidative DNA damage, impacting upon genome stability and thus hepatocarcinogenesis.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.059485-0
2014-05-01
2024-11-03
Loading full text...

Full text loading...

/deliver/fulltext/jgv/95/5/991.html?itemId=/content/journal/jgv/10.1099/vir.0.059485-0&mimeType=html&fmt=ahah

References

  1. Alisi A., Giambartolomei S., Cupelli F., Merlo P., Fontemaggi G., Spaziani A., Balsano C. 2003; Physical and functional interaction between HCV core protein and the different p73 isoforms. Oncogene 22:2573–2580 [View Article][PubMed]
    [Google Scholar]
  2. Ariumi Y., Kuroki M., Dansako H., Abe K., Ikeda M., Wakita T., Kato N. 2008; The DNA damage sensors ataxia-telangiectasia mutated kinase and checkpoint kinase 2 are required for hepatitis C virus RNA replication. J Virol 82:9639–9646 [View Article][PubMed]
    [Google Scholar]
  3. Asselah T., Bièche I., Mansouri A., Laurendeau I., Cazals-Hatem D., Feldmann G., Bedossa P., Paradis V., Martinot-Peignoux M.other authors 2010; In vivo hepatic endoplasmic reticulum stress in patients with chronic hepatitis C. J Pathol 221:264–274 [View Article][PubMed]
    [Google Scholar]
  4. Bae I., Fan S., Meng Q., Rih J. K., Kim H. J., Kang H. J., Xu J., Goldberg I. D., Jaiswal A. K., Rosen E. M. 2004; BRCA1 induces antioxidant gene expression and resistance to oxidative stress. Cancer Res 64:7893–7909 [View Article][PubMed]
    [Google Scholar]
  5. Bolukbas C., Bolukbas F. F., Horoz M., Aslan M., Celik H., Erel O. 2005; Increased oxidative stress associated with the severity of the liver disease in various forms of hepatitis B virus infection. BMC Infect Dis 5:95 [View Article][PubMed]
    [Google Scholar]
  6. Boudreau H. E., Emerson S. U., Korzeniowska A., Jendrysik M. A., Leto T. L. 2009; Hepatitis C virus (HCV) proteins induce NADPH oxidase 4 expression in a transforming growth factor beta-dependent manner: a new contributor to HCV-induced oxidative stress. J Virol 83:12934–12946 [View Article][PubMed]
    [Google Scholar]
  7. Bréchot C. 2004; Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new paradigms. Gastroenterology 127:Suppl 1S56–S61 [View Article][PubMed]
    [Google Scholar]
  8. Burdette D., Olivarez M., Waris G. 2010; Activation of transcription factor Nrf2 by hepatitis C virus induces the cell-survival pathway. J Gen Virol 91:681–690 [View Article][PubMed]
    [Google Scholar]
  9. Carvajal-Yepes M., Himmelsbach K., Schaedler S., Ploen D., Krause J., Ludwig L., Weiss T., Klingel K., Hildt E. 2011; Hepatitis C virus impairs the induction of cytoprotective Nrf2 target genes by delocalization of small Maf proteins. J Biol Chem 286:8941–8951 [View Article][PubMed]
    [Google Scholar]
  10. Chan C., Wang Y., Chow P. K., Chung A. Y., Ooi L. L., Lee C. G. 2013; Altered binding site selection of p53 transcription cassettes by hepatitis B virus X protein. Mol Cell Biol 33:485–497 [View Article][PubMed]
    [Google Scholar]
  11. Chapman J. R., Taylor M. R., Boulton S. J. 2012; Playing the end game: DNA double-strand break repair pathway choice. Mol Cell 47:497–510 [View Article][PubMed]
    [Google Scholar]
  12. Chen B. P., Li M., Asaithamby A. 2012; New insights into the roles of ATM and DNA-PKcs in the cellular response to oxidative stress. Cancer Lett 327:103–110 [View Article][PubMed]
    [Google Scholar]
  13. Chung T. W., Lee Y. C., Ko J. H., Kim C. H. 2003; Hepatitis B virus X protein modulates the expression of PTEN by inhibiting the function of p53, a transcriptional activator in liver cells. Cancer Res 63:3453–3458[PubMed]
    [Google Scholar]
  14. Dandri M., Burda M. R., Bürkle A., Zuckerman D. M., Will H., Rogler C. E., Greten H., Petersen J. 2002; Increase in de novo HBV DNA integrations in response to oxidative DNA damage or inhibition of poly(ADP-ribosyl)ation. Hepatology 35:217–223 [View Article][PubMed]
    [Google Scholar]
  15. Dang C. V., Li F., Lee L. A. 2005; Could MYC induction of mitochondrial biogenesis be linked to ROS production and genomic instability?. Cell Cycle 4:1465–1466 [View Article][PubMed]
    [Google Scholar]
  16. Demirdag K., Yilmaz S., Ozdarendeli A., Ozden M., Kalkan A., Kilic S. S. 2003; Levels of plasma malondialdehyde and erythrocyte antioxidant enzyme activities in patients with chronic hepatitis B. Hepatogastroenterology 50:766–770[PubMed]
    [Google Scholar]
  17. Deng L., Nagano-Fujii M., Tanaka M., Nomura-Takigawa Y., Ikeda M., Kato N., Sada K., Hotta H. 2006; NS3 protein of Hepatitis C virus associates with the tumour suppressor p53 and inhibits its function in an NS3 sequence-dependent manner. J Gen Virol 87:1703–1713 [View Article][PubMed]
    [Google Scholar]
  18. Deng L., Shoji I., Ogawa W., Kaneda S., Soga T., Jiang D. P., Ide Y. H., Hotta H. 2011; Hepatitis C virus infection promotes hepatic gluconeogenesis through an NS5A-mediated, FoxO1-dependent pathway. J Virol 85:8556–8568 [View Article][PubMed]
    [Google Scholar]
  19. Ding D., Lou X., Hua D., Yu W., Li L., Wang J., Gao F., Zhao N., Ren G.other authors 2012; Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach. PLoS Genet 8:e1003065 [View Article][PubMed]
    [Google Scholar]
  20. El-Serag H. B. 2002; Hepatocellular carcinoma and hepatitis C in the United States. Hepatology 36:Suppl 1S74–S83 [View Article][PubMed]
    [Google Scholar]
  21. Farinati F., Cardin R., Bortolami M., Burra P., Russo F. P., Rugge M., Guido M., Sergio A., Naccarato R. 2007; Hepatitis C virus: from oxygen free radicals to hepatocellular carcinoma. J Viral Hepat 14:821–829[PubMed]
    [Google Scholar]
  22. Ferlay J., Shin H. R., Bray F., Forman D., Mathers C., Parkin D. M. 2010 GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 Lyon, France: International Agency for Research on Cancer;
    [Google Scholar]
  23. Fisher A. B. 2009; Redox signaling across cell membranes. Antioxid Redox Signal 11:1349–1356 [View Article][PubMed]
    [Google Scholar]
  24. Fujita N., Sugimoto R., Ma N., Tanaka H., Iwasa M., Kobayashi Y., Kawanishi S., Watanabe S., Kaito M., Takei Y. 2008; Comparison of hepatic oxidative DNA damage in patients with chronic hepatitis B and C. J Viral Hepat 15:498–507 [View Article][PubMed]
    [Google Scholar]
  25. Gong G., Waris G., Tanveer R., Siddiqui A. 2001; Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappa B. Proc Natl Acad Sci U S A 98:9599–9604 [View Article][PubMed]
    [Google Scholar]
  26. Graves J. A., Metukuri M., Scott D., Rothermund K., Prochownik E. V. 2009; Regulation of reactive oxygen species homeostasis by peroxiredoxins and c-Myc. J Biol Chem 284:6520–6529 [View Article][PubMed]
    [Google Scholar]
  27. Güngör N., Godschalk R. W., Pachen D. M., Van Schooten F. J., Knaapen A. M. 2007; Activated neutrophils inhibit nucleotide excision repair in human pulmonary epithelial cells: role of myeloperoxidase. FASEB J 21:2359–2367 [View Article][PubMed]
    [Google Scholar]
  28. Guo Z., Deshpande R., Paull T. T. 2010; ATM activation in the presence of oxidative stress. Cell Cycle 9:4805–4811 [View Article][PubMed]
    [Google Scholar]
  29. Gwak G. Y., Lee D. H., Moon T. G., Choi M. S., Lee J. H., Koh K. C., Paik S. W., Park C. K., Joh J. W., Yoo B. C. 2008; The correlation of hepatitis B virus PreS mutation with cellular oxidative DNA damage in hepatocellular carcinoma. Hepatogastroenterology 55:2028–2032[PubMed]
    [Google Scholar]
  30. Hagen T. M., Huang S., Curnutte J., Fowler P., Martinez V., Wehr C. M., Ames B. N., Chisari F. V. 1994; Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma. Proc Natl Acad Sci U S A 91:12808–12812 [View Article][PubMed]
    [Google Scholar]
  31. Higgs M. R., Lerat H., Pawlotsky J. M. 2010; Downregulation of Gadd45beta expression by hepatitis C virus leads to defective cell cycle arrest. Cancer Res 70:4901–4911 [View Article][PubMed]
    [Google Scholar]
  32. Higgs M. R., Lerat H., Pawlotsky J. M. 2012; Hepatitis C virus-induced activation of beta-catenin promotes c-Myc expression and a cascade of pro-carcinogenetic events. Oncogene 32:4683–4693 [View Article][PubMed]
    [Google Scholar]
  33. Hirotsu Y., Katsuoka F., Funayama R., Nagashima T., Nishida Y., Nakayama K., Engel J. D., Yamamoto M. 2012; Nrf2-MafG heterodimers contribute globally to antioxidant and metabolic networks. Nucleic Acids Res 40:10228–10239 [View Article][PubMed]
    [Google Scholar]
  34. Hsieh Y. H., Su I. J., Wang H. C., Chang W. W., Lei H. Y., Lai M. D., Chang W. T., Huang W. 2004; Pre-S mutant surface antigens in chronic hepatitis B virus infection induce oxidative stress and DNA damage. Carcinogenesis 25:2023–2032 [View Article][PubMed]
    [Google Scholar]
  35. Hu L., Chen L., Yang G., Li L., Sun H., Chang Y., Tu Q., Wu M., Wang H. 2011; HBx sensitizes cells to oxidative stress-induced apoptosis by accelerating the loss of Mcl-1 protein via caspase-3 cascade. Mol Cancer 10:43 [View Article][PubMed]
    [Google Scholar]
  36. Hussain S. P., Hofseth L. J., Harris C. C. 2003; Radical causes of cancer. Nat Rev Cancer 3:276–285 [View Article][PubMed]
    [Google Scholar]
  37. Ishikawa M., Numazawa S., Yoshida T. 2005; Redox regulation of the transcriptional repressor Bach1. Free Radic Biol Med 38:1344–1352 [View Article][PubMed]
    [Google Scholar]
  38. Ito K., Arai M., Imazeki F., Yonemitsu Y., Bekku D., Kanda T., Fujiwara K., Fukai K., Sato K.other authors 2010; Risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Scand J Gastroenterol 45:243–249 [View Article][PubMed]
    [Google Scholar]
  39. Ivanov A. V., Smirnova O. A., Ivanova O. N., Masalova O. V., Kochetkov S. N., Isaguliants M. G. 2011; Hepatitis C virus proteins activate NRF2/ARE pathway by distinct ROS-dependent and independent mechanisms in HUH7 cells. PloS One 6:e24957 [View Article][PubMed]
    [Google Scholar]
  40. Ivanov A. V., Bartosch B., Smirnova O. A., Isaguliants M. G., Kochetkov S. N. 2013; HCV and oxidative stress in the liver. Viruses 5:439–469 [View Article][PubMed]
    [Google Scholar]
  41. Jaeschke H. 2011; Reactive oxygen and mechanisms of inflammatory liver injury: Present concepts. J Gastroenterol Hepatol 26:Suppl 1173–179 [View Article][PubMed]
    [Google Scholar]
  42. Jaitovich-Groisman I., Benlimame N., Slagle B. L., Perez M. H., Alpert L., Song D. J., Fotouhi-Ardakani N., Galipeau J., Alaoui-Jamali M. A. 2001; Transcriptional regulation of the TFIIH transcription repair components XPB and XPD by the hepatitis B virus x protein in liver cells and transgenic liver tissue. J Biol Chem 276:14124–14132[PubMed]
    [Google Scholar]
  43. Jia L., Wang X. W., Harris C. C. 1999; Hepatitis B virus X protein inhibits nucleotide excision repair. Int J Cancer 80:875–879 [View Article][PubMed]
    [Google Scholar]
  44. Kao C.-F., Chen S.-Y., Chen J.-Y., Wu Lee Y.-H. 2004; Modulation of p53 transcription regulatory activity and post-translational modification by hepatitis C virus core protein. Oncogene 23:2472–2483 [View Article][PubMed]
    [Google Scholar]
  45. Karlsson A., Deb-Basu D., Cherry A., Turner S., Ford J., Felsher D. W. 2003; Defective double-strand DNA break repair and chromosomal translocations by MYC overexpression. Proc Natl Acad Sci U S A 100:9974–9979 [View Article][PubMed]
    [Google Scholar]
  46. Kato J., Kobune M., Nakamura T., Kuroiwa G., Takada K., Takimoto R., Sato Y., Fujikawa K., Takahashi M.other authors 2001; Normalization of elevated hepatic 8-hydroxy-2′-deoxyguanosine levels in chronic hepatitis C patients by phlebotomy and low iron diet. Cancer Res 61:8697–8702[PubMed]
    [Google Scholar]
  47. Kim H. J., Kim S. Y., Kim J., Lee H., Choi M., Kim J. K., Ahn J. K. 2008; Hepatitis B virus X protein induces apoptosis by enhancing translocation of Bax to mitochondria. IUBMB Life 60:473–480 [View Article][PubMed]
    [Google Scholar]
  48. Koike K. 2007; Hepatitis C virus contributes to hepatocarcinogenesis by modulating metabolic and intracellular signaling pathways. J Gastroenterol Hepatol 22:Suppl 1S108–S111 [View Article][PubMed]
    [Google Scholar]
  49. Konishi M., Iwasa M., Araki J., Kobayashi Y., Katsuki A., Sumida Y., Nakagawa N., Kojima Y., Watanabe S.other authors 2006; Increased lipid peroxidation in patients with non-alcoholic fatty liver disease and chronic hepatitis C as measured by the plasma level of 8-isoprostane. J Gastroenterol Hepatol 21:1821–1825 [View Article][PubMed]
    [Google Scholar]
  50. Korenaga M., Wang T., Li Y., Showalter L. A., Chan T., Sun J., Weinman S. A. 2005; Hepatitis C virus core protein inhibits mitochondrial electron transport and increases reactive oxygen species (ROS) production. J Biol Chem 280:37481–37488 [View Article][PubMed]
    [Google Scholar]
  51. Kuraoka I., Bender C., Romieu A., Cadet J., Wood R. D., Lindahl T. 2000; Removal of oxygen free-radical-induced 5′,8-purine cyclodeoxynucleosides from DNA by the nucleotide excision-repair pathway in human cells. Proc Natl Acad Sci U S A 97:3832–3837 [View Article][PubMed]
    [Google Scholar]
  52. Kwun H. J., Jang K. L. 2003; Dual effects of hepatitis C virus Core protein on the transcription of cyclin-dependent kinase inhibitor p21 gene. J Viral Hepat 10:249–255 [View Article][PubMed]
    [Google Scholar]
  53. Lan K.-H., Sheu M.-L., Hwang S.-J., Yen S.-H., Chen S.-Y., Wu J.-C., Wang Y.-J., Kato N., Omata M.other authors 2002; HCV NS5A interacts with p53 and inhibits p53-mediated apoptosis. Oncogene 21:4801–4811 [View Article][PubMed]
    [Google Scholar]
  54. Le Page F., Randrianarison V., Marot D., Cabannes J., Perricaudet M., Feunteun J., Sarasin A. 2000; BRCA1 and BRCA2 are necessary for the transcription-coupled repair of the oxidative 8-oxoguanine lesion in human cells. Cancer Res 60:5548–5552[PubMed]
    [Google Scholar]
  55. Lee Y. I., Hwang J. M., Im J. H., Lee Y. I., Kim N. S., Kim D. G., Yu D. Y., Moon H. B., Park S. K. 2004; Human hepatitis B virus-X protein alters mitochondrial function and physiology in human liver cells. J Biol Chem 279:15460–15471 [View Article][PubMed]
    [Google Scholar]
  56. Lee A. T., Ren J., Wong E. T., Ban K. H., Lee L. A., Lee C. G. 2005; The hepatitis B virus X protein sensitizes HepG2 cells to UV light-induced DNA damage. J Biol Chem 280:33525–33535 [View Article][PubMed]
    [Google Scholar]
  57. Lerat H., Kammoun H. L., Hainault I., Mérour E., Higgs M. R., Callens C., Lemon S. M., Foufelle F., Pawlotsky J. M. 2009; Hepatitis C virus proteins induce lipogenesis and defective triglyceride secretion in transgenic mice. J Biol Chem 284:33466–33474 [View Article][PubMed]
    [Google Scholar]
  58. Lerat H., Higgs M., Pawlotsky J. M. 2011; Animal models in the study of hepatitis C virus-associated liver pathologies. Expert Rev Gastroenterol Hepatol 5:341–352 [View Article][PubMed]
    [Google Scholar]
  59. Li K., Prow T., Lemon S. M., Beard M. R. 2002; Cellular response to conditional expression of hepatitis C virus core protein in Huh7 cultured human hepatoma cells. Hepatology 35:1237–1246 [View Article][PubMed]
    [Google Scholar]
  60. Li S., Ye L., Yu X., Xu B., Li K., Zhu X., Liu H., Wu X., Kong L. 2009; Hepatitis C virus NS4B induces unfolded protein response and endoplasmic reticulum overload response-dependent NF-kappaB activation. Virology 391:257–264 [View Article][PubMed]
    [Google Scholar]
  61. Lin Y., Nomura T., Yamashita T., Dorjsuren D., Tang H., Murakami S. 1997; The transactivation and p53-interacting functions of hepatitis B virus X protein are mutually interfering but distinct. Cancer Res 57:5137–5142[PubMed]
    [Google Scholar]
  62. Machida K., Cheng K. T.-H., Lai C.-K., Jeng K.-S., Sung V. M.-H., Lai M. M. C. 2006; Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation. J Virol 80:7199–7207 [View Article][PubMed]
    [Google Scholar]
  63. Machida K., Tsukamoto H., Liu J. C., Han Y. P., Govindarajan S., Lai M. M., Akira S., Ou J. H. 2010a; c-Jun mediates hepatitis C virus hepatocarcinogenesis through signal transducer and activator of transcription 3 and nitric oxide-dependent impairment of oxidative DNA repair. Hepatology 52:480–492 [View Article][PubMed]
    [Google Scholar]
  64. Machida K., McNamara G., Cheng K. T., Huang J., Wang C. H., Comai L., Ou J. H., Lai M. M. 2010b; Hepatitis C virus inhibits DNA damage repair through reactive oxygen and nitrogen species and by interfering with the ATM-NBS1/Mre11/Rad50 DNA repair pathway in monocytes and hepatocytes. J Immunol 185:6985–6998 [View Article][PubMed]
    [Google Scholar]
  65. Mahmood S., Kawanaka M., Kamei A., Izumi A., Nakata K., Niiyama G., Ikeda H., Hanano S., Suehiro M.other authors 2004; Immunohistochemical evaluation of oxidative stress markers in chronic hepatitis C. Antioxid Redox Signal 6:19–24 [View Article][PubMed]
    [Google Scholar]
  66. Mathonnet G., Lachance S., Alaoui-Jamali M., Drobetsky E. A. 2004; Expression of hepatitis B virus X oncoprotein inhibits transcription-coupled nucleotide excision repair in human cells. Mutat Res 554:305–318 [View Article][PubMed]
    [Google Scholar]
  67. Menoni H., Hoeijmakers J. H., Vermeulen W. 2012; Nucleotide excision repair-initiating proteins bind to oxidative DNA lesions in vivo. J Cell Biol 199:1037–1046 [View Article][PubMed]
    [Google Scholar]
  68. Miao J., Chen G. G., Chun S. Y., Lai P. P. 2006; Hepatitis B virus X protein induces apoptosis in hepatoma cells through inhibiting Bcl-xL expression. Cancer Lett 236:115–124 [View Article][PubMed]
    [Google Scholar]
  69. Miura K., Taura K., Kodama Y., Schnabl B., Brenner D. A. 2008; Hepatitis C virus-induced oxidative stress suppresses hepcidin expression through increased histone deacetylase activity. Hepatology 48:1420–1429 [View Article][PubMed]
    [Google Scholar]
  70. Moriya K., Nakagawa K., Santa T., Shintani Y., Fujie H., Miyoshi H., Tsutsumi T., Miyazawa T., Ishibashi K.other authors 2001; Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis. Cancer Res 61:4365–4370[PubMed]
    [Google Scholar]
  71. Naik E., Dixit V. M. 2011; Mitochondrial reactive oxygen species drive proinflammatory cytokine production. J Exp Med 208:417–420 [View Article][PubMed]
    [Google Scholar]
  72. Nishina S., Hino K., Korenaga M., Vecchi C., Pietrangelo A., Mizukami Y., Furutani T., Sakai A., Okuda M.other authors 2008; Hepatitis C virus-induced reactive oxygen species raise hepatic iron level in mice by reducing hepcidin transcription. Gastroenterology 134:226–238 [View Article][PubMed]
    [Google Scholar]
  73. Okuda M., Li K., Beard M. R., Showalter L. A., Scholle F., Lemon S. M., Weinman S. A. 2002; Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 122:366–375 [View Article][PubMed]
    [Google Scholar]
  74. Pal S., Polyak S. J., Bano N., Qiu W. C., Carithers R. L., Shuhart M., Gretch D. R., Das A. 2010; Hepatitis C virus induces oxidative stress, DNA damage and modulates the DNA repair enzyme NEIL1. J Gastroenterol Hepatol 25:627–634 [View Article][PubMed]
    [Google Scholar]
  75. Perz J. F., Armstrong G. L., Farrington L. A., Hutin Y. J., Bell B. P. 2006; The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 45:529–538 [View Article][PubMed]
    [Google Scholar]
  76. Piccoli C., Scrima R., Quarato G., D’Aprile A., Ripoli M., Lecce L., Boffoli D., Moradpour D., Capitanio N. 2007; Hepatitis C virus protein expression causes calcium-mediated mitochondrial bioenergetic dysfunction and nitro-oxidative stress. Hepatology 46:58–65 [View Article][PubMed]
    [Google Scholar]
  77. Qadri I., Fatima K., Abdel-Hafiz H. 2011; Hepatitis B virus X protein impedes the DNA repair via its association with transcription factor, TFIIH. BMC Microbiol 11:48 [View Article][PubMed]
    [Google Scholar]
  78. Ray S., Atkuri K. R., Deb-Basu D., Adler A. S., Chang H. Y., Herzenberg L. A., Felsher D. W. 2006; MYC can induce DNA breaks in vivo and in vitro independent of reactive oxygen species. Cancer Res 66:6598–6605 [View Article][PubMed]
    [Google Scholar]
  79. Reardon J. T., Bessho T., Kung H. C., Bolton P. H., Sancar A. 1997; In vitro repair of oxidative DNA damage by human nucleotide excision repair system: possible explanation for neurodegeneration in xeroderma pigmentosum patients. Proc Natl Acad Sci U S A 94:9463–9468 [View Article][PubMed]
    [Google Scholar]
  80. Rivas-Estilla A. M., Bryan-Marrugo O. L., Trujillo-Murillo K., Pérez-Ibave D., Charles-Niño C., Pedroza-Roldan C., Ríos-Ibarra C., Ramírez-Valles E., Ortiz-López R.other authors 2012; Cu/Zn superoxide dismutase (SOD1) induction is implicated in the antioxidative and antiviral activity of acetylsalicylic acid in HCV-expressing cells. Am J Physiol Gastrointest Liver Physiol 302:G1264–G1273 [View Article][PubMed]
    [Google Scholar]
  81. Saito I., Miyamura T., Ohbayashi A., Harada H., Katayama T., Kikuchi S., Watanabe Y., Koi S., Onji M., Ohta Y. 1990; Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc Natl Acad Sci U S A 87:6547–6549 [View Article][PubMed]
    [Google Scholar]
  82. Schaedler S., Krause J., Himmelsbach K., Carvajal-Yepes M., Lieder F., Klingel K., Nassal M., Weiss T. S., Werner S., Hildt E. 2010; Hepatitis B virus induces expression of antioxidant response element-regulated genes by activation of Nrf2. J Biol Chem 285:41074–41086 [View Article][PubMed]
    [Google Scholar]
  83. Schults M. A., Nagle P. W., Rensen S. S., Godschalk R. W., Munnia A., Peluso M., Claessen S. M., Greve J. W., Driessen A.other authors 2012; Decreased nucleotide excision repair in steatotic livers associates with myeloperoxidase-immunoreactivity. Mutat Res 736:75–81 [View Article][PubMed]
    [Google Scholar]
  84. Sedelnikova O. A., Redon C. E., Dickey J. S., Nakamura A. J., Georgakilas A. G., Bonner W. M. 2010; Role of oxidatively induced DNA lesions in human pathogenesis. Mutat Res 704:152–159 [View Article][PubMed]
    [Google Scholar]
  85. Severi T., Ying C., Vermeesch J. R., Cassiman D., Cnops L., Verslype C., Fevery J., Arckens L., Neyts J., van Pelt J. F. 2006; Hepatitis B virus replication causes oxidative stress in HepAD38 liver cells. Mol Cell Biochem 290:79–85 [View Article][PubMed]
    [Google Scholar]
  86. Shackel N. A., McGuinness P. H., Abbott C. A., Gorrell M. D., McCaughan G. W. 2002; Insights into the pathobiology of hepatitis C virus-associated cirrhosis: analysis of intrahepatic differential gene expression. Am J Pathol 160:641–654 [View Article][PubMed]
    [Google Scholar]
  87. Shirakata Y., Koike K. 2003; Hepatitis B virus X protein induces cell death by causing loss of mitochondrial membrane potential. J Biol Chem 278:22071–22078 [View Article][PubMed]
    [Google Scholar]
  88. Simonetti R. G., Cammà C., Fiorello F., Cottone M., Rapicetta M., Marino L., Fiorentino G., Craxì A., Ciccaglione A.other authors 1992; Hepatitis C virus infection as a risk factor for hepatocellular carcinoma in patients with cirrhosis. A case-control study. Ann Intern Med 116:97–102 [View Article][PubMed]
    [Google Scholar]
  89. Simula M. P., De Re V. 2010; Hepatitis C virus-induced oxidative stress and mitochondrial dysfunction: a focus on recent advances in proteomics. Proteomics Clin Appl 4:782–793 [View Article][PubMed]
    [Google Scholar]
  90. Singal A. K., Jampana S. C., Weinman S. A. 2011; Antioxidants as therapeutic agents for liver disease. Liver Int 31:1432–1448 [View Article][PubMed]
    [Google Scholar]
  91. Smirnova I. S., Aksenov N. D., Vonsky M. S., Isaguliants M. G. 2006; Different transformation pathways of murine fibroblast NIH 3T3 cells by hepatitis C virus core and NS3 proteins. Cell Biol Int 30:915–919 [View Article][PubMed]
    [Google Scholar]
  92. Takada S., Shirakata Y., Kaneniwa N., Koike K. 1999; Association of hepatitis B virus X protein with mitochondria causes mitochondrial aggregation at the nuclear periphery, leading to cell death. Oncogene 18:6965–6973 [View Article][PubMed]
    [Google Scholar]
  93. Toh S. T., Jin Y., Liu L., Wang J., Babrzadeh F., Gharizadeh B., Ronaghi M., Toh H. C., Chow P. K.other authors 2013; Deep sequencing of the hepatitis B virus in hepatocellular carcinoma patients reveals enriched integration events, structural alterations and sequence variations. Carcinogenesis 34:787–798 [View Article][PubMed]
    [Google Scholar]
  94. Vafa O., Wade M., Kern S., Beeche M., Pandita T. K., Hampton G. M., Wahl G. M. 2002; c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53 function: a mechanism for oncogene-induced genetic instability. Mol Cell 9:1031–1044 [View Article][PubMed]
    [Google Scholar]
  95. van de Klundert M. A., van Hemert F. J., Zaaijer H. L., Kootstra N. A. 2012; The hepatitis B virus x protein inhibits thymine DNA glycosylase initiated base excision repair. PLoS ONE 7:e48940 [View Article][PubMed]
    [Google Scholar]
  96. Vurusaner B., Poli G., Basaga H. 2012; Tumor suppressor genes and ROS: complex networks of interactions. Free Radic Biol Med 52:7–18 [View Article][PubMed]
    [Google Scholar]
  97. Wang T., Weinman S. A. 2006; Causes and consequences of mitochondrial reactive oxygen species generation in hepatitis C. J Gastroenterol Hepatol 21:Suppl 3S34–S37 [View Article][PubMed]
    [Google Scholar]
  98. Wang T., Weinman S. A. 2013; Interactions between hepatitis C virus and mitochondria: impact on pathogenesis and innate immunity. Curr Pathobiol Rep 1:179–187 [View Article][PubMed]
    [Google Scholar]
  99. Wang X. W., Forrester K., Yeh H., Feitelson M. A., Gu J. R., Harris C. C. 1994; Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. Proc Natl Acad Sci U S A 91:2230–2234 [View Article][PubMed]
    [Google Scholar]
  100. Wang H. C., Chang W. T., Chang W. W., Wu H. C., Huang W., Lei H. Y., Lai M. D., Fausto N., Su I. J. 2005; Hepatitis B virus pre-S2 mutant upregulates cyclin A expression and induces nodular proliferation of hepatocytes. Hepatology 41:761–770 [View Article][PubMed]
    [Google Scholar]
  101. Wang A. G., Lee D. S., Moon H. B., Kim J. M., Cho K. H., Choi S. H., Ha H. L., Han Y. H., Kim D. G.other authors 2009; Non-structural 5A protein of hepatitis C virus induces a range of liver pathology in transgenic mice. J Pathol 219:253–262 [View Article][PubMed]
    [Google Scholar]
  102. Woodbine L., Brunton H., Goodarzi A. A., Shibata A., Jeggo P. A. 2011; Endogenously induced DNA double strand breaks arise in heterochromatic DNA regions and require ataxia telangiectasia mutated and Artemis for their repair. Nucleic Acids Res 39:6986–6997 [View Article][PubMed]
    [Google Scholar]
  103. Yamanaka T., Kodama T., Doi T. 2002; Subcellular localization of HCV core protein regulates its ability for p53 activation and p21 suppression. Biochem Biophys Res Commun 294:528–534 [View Article][PubMed]
    [Google Scholar]
  104. Yun C., Lee J. H., Park H., Jin Y. M., Park S., Park K., Cho H. 2000; Chemotherapeutic drug, adriamycin, restores the function of p53 protein in hepatitis B virus X (HBx) protein-expressing liver cells. Oncogene 19:5163–5172 [View Article][PubMed]
    [Google Scholar]
/content/journal/jgv/10.1099/vir.0.059485-0
Loading
/content/journal/jgv/10.1099/vir.0.059485-0
Loading

Data & Media loading...

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