Modern views on the role of X gene of the hepatitis B virus (Hepadnaviridae: Orthohepadnavirus: Hepatitis B virus) in the pathogenesis of the infection it causes

Cover Image

Cite item

Full Text

Abstract

The review presents information on the role of hepatitis B virus (Hepadnaviridae: Orthohepadnavirus: Hepatitis B virus) (HBV) X gene and the protein it encodes (X protein) in the pathogenesis of viral hepatitis B. The evolution of HBV from primordial to the modern version of hepadnaviruses (Hepadnaviridae), is outlined as a process that began about 407 million years ago and continues to the present. The results of scientific works of foreign researchers on the variety of the influence of X protein on the infectious process and its role in the mechanisms of carcinogenesis are summarized. The differences in the effect of the X protein on the course of the disease in patients of different ethnic groups with regard to HBV genotypes are described. The significance of determining the genetic variability of X gene as a fundamental characteristic of the virus that has significance for the assessment of risks of hepatocellular carcinoma (HCC) spread among the population of the Russian Federation is discussed.

About the authors

Y. V. Panasiuk

FSBI «Central Research Institute for Epidemiology» of the Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor)

Author for correspondence.
Email: epidbsmp@mail.ru
ORCID iD: 0000-0002-9335-4953

Panasiuk Ya.V., Physician-Epidemiologist of the Viral Hepatitis Laboratory, Department of Molecular Diagnostics and Epidemiology

Moscow, 111123

Russian Federation

N. V. Vlasenko

FSBI «Central Research Institute for Epidemiology» of the Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor)

Email: fake@neicon.ru
ORCID iD: 0000-0002-2388-1483

Moscow, 111123

Russian Federation

N. S. Churilova

FSBI «Central Research Institute for Epidemiology» of the Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor)

Email: fake@neicon.ru
ORCID iD: 0000-0001-5344-5829

Moscow, 111123

Russian Federation

V. V. Klushkina

FSBI «Central Research Institute for Epidemiology» of the Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor)

Email: fake@neicon.ru
ORCID iD: 0000-0001-8311-8204

Moscow, 111123

Russian Federation

D. V. Dubodelov

FSBI «Central Research Institute for Epidemiology» of the Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor)

Email: fake@neicon.ru
ORCID iD: 0000-0003-3093-5731

Moscow, 111123

Russian Federation

E. N. Kudryavtseva

FSBI «Central Research Institute for Epidemiology» of the Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor)

Email: fake@neicon.ru
ORCID iD: 0000-0002-7325-8577

Moscow, 111123

Russian Federation

M. I. Korabelnikova

FSBI «Central Research Institute for Epidemiology» of the Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor)

Email: fake@neicon.ru
ORCID iD: 0000-0002-2575-8569

Moscow, 111123

Russian Federation

Z. S. Rodionova

FSBI «Central Research Institute for Epidemiology» of the Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor)

Email: fake@neicon.ru
ORCID iD: 0000-0002-2575-8569

Moscow, 111123

Russian Federation

T. A. Semenenko

FSBI «National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya» of the Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-6686-9011

123098, Moscow

Russian Federation

S. N. Kuzin

FSBI «Central Research Institute for Epidemiology» of the Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor)

Email: fake@neicon.ru
ORCID iD: 0000-0002-0616-9777

Moscow, 111123

Russian Federation

V. G. Akimkin

FSBI «Central Research Institute for Epidemiology» of the Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor)

Email: fake@neicon.ru
ORCID iD: 0000-0003-4228-9044

Moscow, 111123

Russian Federation

References

  1. WHO. Hepatitis B: Fact sheet. Available at: https://www.who.int/newsroom/fact-sheets/detail/hepatitis-b (accessed November 29, 2021).
  2. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., et.al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2020; 71(3): 209–49. https://doi.org/10.3322/caac.21660
  3. Ющук Н.Д., Климова Е.А., Знойко О.О., Кареткина Г.Н., Максимов С.Л., Маев И.В. Вирусные гепатиты: клиника, диагностика, лечение. М.: ГЭОТАР-Медиа; 2014.
  4. Revill P.A., Tu T., Netter H.J., Yuen L.K.W., Locarnini S.A., Littlejohn M. The evolution and clinical impact of hepatitis B virus genome diversity. Nat. Rev. Gastroenterol. Hepatol. 2020; 17(10): 618–34. https://doi.org/10.1038/s41575-020-0296-6
  5. Datta S. An overview of molecular epidemiology of hepatitis B virus (HBV) in India. Virol. J. 2008; 5: 156. https://doi.org/10.1186/1743-422X-5-156
  6. Tuteja A., Siddiqui A.B., Madan K., Goyal R., Shalimar, Sreenivas V., et al. Mutation profiling of the hepatitis B virus strains circulating in North Indian population. PLoS One. 2014; 9(3): e91150. https://doi.org/10.1371/journal.pone.0091150
  7. Tarocchi M., Polvani S., Marroncini G., Galli A. Molecular mechanism of hepatitis B virus-induced hepatocarcinogenesis. World J. Gastroenterol. 2014; 20(33): 11630–40. https://doi.org/10.3748/wjg.v20.i33.11630
  8. Levrero M., Zucman-Rossi J. Mechanisms of HBV-induced hepatocellular carcinoma. J. Hepatol. 2016; 64(1 Suppl.): S84–101. https://doi.org/10.1016/j.jhep.2016.02.021
  9. Lau K.C.K., Burak K.W., Coffin C.S. Impact of hepatitis B virus genetic variation, integration, and lymphotropism in antiviral treatment and oncogenesis. Microorganisms. 2020; 8(10): 1470. https://doi.org/10.3390/microorganisms8101470
  10. Godoy C., Tabernero D., Sopena S., Gregori J., Cortese M.F., González C., et al. Characterization of hepatitis B virus X gene quasispecies complexity in mono-infection and hepatitis delta virus superinfection. World J. Gastroenterol. 2019; 25(13): 1566–79. https://doi.org/10.3748/wjg.v25.i13.1566
  11. Sung W.K., Lu Y., Lee C.W.H., Zhang D., Ronaghi M., Lee C.G.L. Deregulated direct targets of the hepatitis B virus (HBV) protein, HBx, identified through chromatin immunoprecipitation and expression microarray profiling. J. Biol. Chem. 2009; 284(33): 21941–54. https://doi.org/10.1074/jbc.M109.014563
  12. van Hemert F.J., van de Klundert M.A.A., Lukashov V.V., Kootstra N.A., Berkhout B., Zaaijer H.L., et al. Protein X of hepatitis B virus: origin and structure similarity with the central domain of DNA glycosylase. PLoS One. 2011; 6(8): e23392. https://doi.org/10.1371/journal.pone.0023392
  13. Al-Qahtani A.A., Al-Anazi M.R., Nazir N., Ghai R., Abdo A.A., Sanai F.M., et al. Hepatitis B virus (HBV) X gene mutations and their association with liver disease progression in HBV-infected patients. Oncotarget. 2017; 8(62): 105115–25. https://doi.org/10.18632/oncotarget.22428
  14. Rahmani Z., Huh K.W., Lasher R., Siddiqui A. Hepatitis B virus X protein colocalizes to mitochondria with a human voltage-dependent anion channel, HVDAC3, and alters its transmembrane potential. J. Virol. 2000; 74(6): 2840–6. https://doi.org/10.1128/jvi.74.6.2840-2846.2000
  15. Salpini R., Surdo M., Cortese M.F., Palumbo G.A., Carioti L., Cappiello G., et al The novel HBx mutation F30V correlates with hepatocellular carcinoma in vivo, reduces hepatitis B virus replicative efficiency and enhances anti-apoptotic activity of HBx N terminus in vitro. Clin. Microbiol. Infect. 2019; 25(7): 906.e1–7. https://doi.org/10.1016/j.cmi.2018.11.017
  16. Chang S.F., Netter H.J., Hildt E., Schuster R., Schaefer S., Hsu Y.C., et al. Duck hepatitis B virus expresses a regulatory HBx-like protein from a hidden open reading frame. J. Virol. 2001; 75(1): 161–70. https://doi.org/10.1128/JVI.75.1.161-170.2001
  17. Bouchard M.J., Schneider R.J. The enigmatic X gene of hepatitis B virus. J. Virol. 2004; 78(23): 12725–34. https://doi.org/10.1128/JVI.78.23.12725-12734.2004
  18. Gómez-Gonzalo M., Carretero M., Rullas J., Lara-Pezzi E., Aramburu J., Berkhout B., et al. The hepatitis B virus X protein induces HIV-1 replication and transcription in synergy with T-cell activation signals: functional roles of NF-κB/NF-AT and SP1-binding sites in the HIV-1 long terminal repeat promoter. J. Biol. Chem. 2001; 276(38): 35435–43. https://doi.org/10.1074/jbc.M103020200
  19. González C., Tabernero D., Cortese M.F., Gregori J., Casillas R., Riveiro-Barciela M., et al. Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy. World J. Gastroenterol. 2018; 24(19): 2095–107. https://doi.org/10.3748/wjg.v24.i19.2095
  20. Kim H., Lee S.A., Kim B.J. X region mutations of hepatitis B virus related to clinical severity. World J. Gastroenterol. 2016; 22(24): 5467–78. https://doi.org/10.3748/wjg.v22.i24.5467
  21. Suh A., Brosius J., Schmitz J., Kriegs J.O. The genome of a Mesozoic paleovirus reveals the evolution of hepatitis B viruses. Nat. Commun. 2013; 4: 1791. https://doi.org/10.1038/ncomms2798
  22. Suh A., Weber C.C., Kehlmaier C., Braun E.L., Green R.E., Fritz U., et al. Early Mesozoic Coexistence of Amniotes and Hepadnaviridae. PLoS Genet. 2014; 10(12): e1004559. https://doi.org/10.1371/journal.pgen.1004559
  23. Lauber C., Seitz S., Mattei S., Suh A., Beck J., Herstein J., et al. Deciphering the origin and evolution of hepatitis B viruses by means of a family of non-enveloped fish viruses. Cell Host Microbe. 2017; 22(3): 387–99.e6. https://doi.org/10.1016/j.chom.2017.07.0192
  24. Pesavento P.A., Jackson K., Scase T., Tse T., Hampson B., Munday J.S., et al. A novel hepadnavirus is associated with chronic hepatitis and hepatocellular carcinoma in cats. Viruses. 2019; 11(10): 969. https://doi.org/10.3390/v11100969
  25. Bonvicino C.R., Moreira M.A., Soares M.A. Hepatitis B virus lineages in mammalian hosts: potential for bidirectional cross-species transmission. World J. Gastroenterol. 2014; 20(24): 7665–74. https://doi.org/10.3748/wjg.v20.i24.7665
  26. Hu X., Javadian A., Gagneux P., Robertson B.H. Paired chimpanzee hepatitis B virus (ChHBV) and mtDNA sequences suggest different ChHBV genetic variants are found in geographically distinct chimpanzee subspecies. Virus. Res. 2001; 79(1-2): 103–8. https://doi.org/10.1016/s0168-1702(01)00334-3
  27. He B., Fan Q., Yang F., Hu T., Qiu W., Feng Y., et al. Hepatitis virus in long-fingered bats, Myanmar. Emerg. Infect. Dis. 2013; 19(4): 638–40. https://doi.org/10.3201/eid1904.121655
  28. Li W., She R., Liu L., You H., Yin J. Prevalence of a virus similar to human hepatitis B virus in swine. Virol. J. 2010; 7: 60. https://doi.org/10.1186/1743-422x-7-60
  29. Sa-Nguanmoo P., Rianthavorn P., Amornsawadwattana S., Poovorawan Y. Hepatitis B virus infection in non-human primates. Acta Virol. 2009; 53(2): 73–82. https://doi.org/10.4149/av_2009_02_73
  30. Lanford R.E., Chavez D., Brasky K.M., Burns R.B. III, Rico-Hesse R. Isolation of a hepadnavirus from the woolly monkey, a New World primate. Proc. Natl Acad. Sci. USA. 1998; 95(10): 5757–61. https://doi.org/10.1073/pnas.95.10.5757
  31. Tian J., Xia K., She R., Li W., Ding Y., Wang J., et al. Detection of Hepatitis B virus in serum and liver of chickens. Virol. J. 2012; 9: 2. https://doi.org/10.1186/1743-422X-9-2
  32. Summers J., Smolec J.M., Snyder R. A virus similar to human hepatitis B virus associated with hepatitis and hepatoma in woodchucks. Proc. Natl Acad. Sci. USA. 1978; 75(9): 4533–7. https://doi.org/10.1073/pnas.75.9.4533
  33. Mason W.S., Seal G., Summers J. Virus of Pekin ducks with structural and biological relatedness to human hepatitis B virus. J. Virol. 1980; 36(3): 829–36. https://doi.org/10.1128/JVI.36.3.829-836.1980
  34. Sprengel R., Kaleta E.F., Will H. Isolation and characterization of a hepatitis B virus endemic in herons. J. Virol. 1988; 62(10): 3832–9. https://doi.org/10.1128/JVI.62.10.3832-3839.1988
  35. Chang S.F., Netter H.J., Bruns M., Schneider R., Frölich K., Will H. A new avian hepadnavirus infecting snow geese (Anser caerulescens) produces a significant fraction of virions containing single-stranded DNA. Virology. 1999; 262(1): 39–54. https://doi.org/10.1006/viro.1999.9844
  36. Pult I., Netter H.J., Bruns M., Prassolov A., Sirma H., Hohenberg H., et al. Identification and analysis of a new hepadnavirus in white storks. Virology. 2001; 289(1): 114–28. https://doi.org/10.1006/viro.2001.1115
  37. Prassolov A., Hohenberg H., Kalinina T., Schneider C., Cova L., Krone O., et al. New hepatitis B virus of cranes that has an unexpected broad host range. J. Virol. 2003; 77(3): 1964–76. https://doi.org/10.1128/jvi.77.3.1964-1976.2003
  38. Lauber C., Seitz S., Mattei S., Suh A., Beck J., Herstein J., et al. Deciphering the origin and evolution of hepatitis B viruses by means of a family of non-enveloped fish viruses. Cell Host Microbe. 2017; 22(3): 387–99.e6. https://doi.org/10.1016/j.chom.2017.07.0192
  39. Meier A., Mehrle S., Weiss T.S., Mier W., Urban S. Myristoylated PreS1-domain of the hepatitis B virus L-protein mediates specific binding to differentiated hepatocytes. Hepatology. 2013; 58(1): 31–42. https://doi.org/10.1002/hep.26181
  40. Kumar V., Jayasuryan N., Kumar R. A truncated mutant (residues 58–140) of the hepatitis B virus X protein retains transactivation function. Proc. Natl Acad. Sci. USA. 1996; 93(11): 5647–52. https://doi.org/10.1073/pnas.93.11.5647
  41. Qadri I., Maguire H.F., Siddiqui A. Hepatitis B virus transactivator protein X interacts with the TATA-binding protein. Proc. Natl Acad. Sci. USA. 1995; 92(4): 1003–7. https://doi.org/10.1073/pnas.92.4.1003
  42. Belloni L., Pollicino T., De Nicola F., Guerrieri F., Raffa G., Fanciulli M., et. al. Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function. Proc. Natl Acad. Sci. USA. 2009; 106(47): 19975–9. https://doi.org/10.1073/pnas.0908365106
  43. Kornyeyev D., Ramakrishnan D., Voitenleitner C., Livingston C.M., Xing W., Hung M., et al. Spatiotemporal analysis of hepatitis B virus X protein in primary human hepatocytes. J. Virol. 2019; 93(16): e00248-19. https://doi.org/10.1128/JVI.00248-19
  44. Ali A., Abdel-Hafiz H., Suhail M., Al-Mars A., Zakaria M.K., Fatima K., et al. Hepatitis B virus, HBx mutants and their role in hepatocellular carcinoma. World J. Gastroenterol. 2014; 20(30): 10238–48. https://doi.org/10.3748/wjg.v20.i30.10238
  45. Taylor E.M., Moghraby J.S., Lees J.H., Smit B., Moens P.B., Lehmann A.R. Characterization of a novel human SMC heterodimer homologous to the Schizosaccharomyces pombe Rad18/Spr18 complex. Mol. Biol. Cell. 2001; 12(6): 1583–94. https://doi.org/10.1091/mbc.12.6.1583
  46. Murphy C.M., Xu Y., Li F., Nio K., Reszka-Blanco N., Li X., et al. Hepatitis B virus X protein promotes degradation of SMC5/6 to enhance HBV replication. Cell Rep. 2016; 16(11): 2846–54. https://doi.org/10.1016/j.celrep.2016.08.026
  47. Abdul F., Filleton F., Gerossier L., Paturel A., Hall J., Strubin M., et al. Smc5/6 Antagonism by HBx Is an Evolutionarily Conserved Function of Hepatitis B Virus Infection in Mammals. J. Virol. 2018; 92(16): e00769-18. https://doi.org/10.1128/JVI.00769-18
  48. Rivière L., Gerossier L., Ducroux A., Dion S., Deng Q., Michel M.L., et al. HBx relieves chromatin-mediated transcriptional repression of hepatitis B viral cccDNA involving SETDB1 histone methyltransferase. J. Hepatol. 2015; 63(5): 1093–102. https://doi.org/10.1016/j.jhep.2015.06.023
  49. Datta S., Banerjee A., Chandra P.K., Biswas A., Panigrahi R., Mahapatra P.K., et al Analysis of hepatitis B virus X gene phylogeny, genetic variability and its impact on pathogenesis: Implications in Eastern Indian HBV carriers. Virology. 2008; 382(2): 190–8. https://doi.org/10.1016/j.virol.2008.09.007
  50. Su F., Schneider R.J. Hepatitis B virus HBx protein sensitizes cells to apoptotic killing by tumor necrosis factor alpha. Proc. Natl Acad. Sci. USA. 1997; 94(16): 8744–9. https://doi.org/10.1073/pnas.94.16.8744
  51. Sung W.K. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma. Nat. Genet. 2012; 44(7): 765–9. https://doi.org/10.1038/ng.2295
  52. Shafritz D.A., Kew M.C. Identification of integrated hepatitis B virus DNA sequences in human hepatocellular carcinomas. Hepatology. 1981; 1(1): 1–8. https://doi.org/10.1002/hep.1840010102
  53. Chauhan R., Michalak T.I. Earliest hepatitis B virus-hepatocyte genome integration: sites, mechanism, and significance in carcinogenesis. Hepatoma Res. 2021; 7: 20. http://doi.org/10.20517/2394-5079.2020.136
  54. Zhang X., You X., Li N., Zhang W., Gagos S., Wang Q. Involvement of hepatitis B virus X gene (HBx) integration in hepatocarcinogenesis via a recombination of HBx/Alu core sequence/subtelomeric DNA. FEBS Lett. 2012; 586(19): 3215–21. https://doi.org/10.1016/j.febslet.2012.06.039
  55. Wang Y., Wang H., Pan S., Hu T., Shen J., Zheng H., et al. Capable infection of hepatitis B virus in diffuse large B-cell lymphoma. J. Cancer. 2018; 9(9): 1575–81. https://doi.org/10.7150/jca.24384
  56. Baghbanian M., Hoseini Mousa S.A., Doosti M., Moghimi M. Association between gastric pathology and hepatitis B virus infection in patients with or without Helicobacter pylori. Asian Pac. J. Cancer Prev. 2019; 20(7): 2177–80. https://doi.org/10.31557/APJCP.2019.20.7.2177
  57. Niedźwiedzka-Rystwej P., Grywalska E., Hrynkiewicz R., Wołącewicz M., Becht R., Roliński J. The double-edged sword role of viruses in gastric cancer. Cancers (Basel). 2020; 12(6): 1680. https://doi.org/10.3390/cancers12061680
  58. Tagieva N.E., Gizatullin R.Z., Zakharyev V.M., Kisselev L.L. A genome-integrated hepatitis B virus DNA in human neuroblastoma. Gene. 1995; 152(2): 277–8. https://doi.org/10.1016/0378-1119(94)00665-f
  59. Schulte L.A., López-Gil J.C., Sainz B. Jr., Hermann P.C. The cancer stem cell in hepatocellular carcinoma. Cancers (Basel). 2020; 12(3): 684. https://doi.org/10.3390/cancers12030684
  60. Sukowati C.H.C., Reyes P.A.C., Tell G., Tiribelli C. Oncogenicity of viral hepatitis B and C in the initiation of hepatic cancer stem cells. Hepatoma Res. 2019; 5: 2. https://doi.org/10.20517/2394-5079.2018.106
  61. Mani S.K.K., Andrisani O. Hepatitis B virus-associated hepatocellular carcinoma and hepatic cancer stem cells. Genes (Basel). 2018; 9(3): 137. https://doi.org/10.3390/genes9030137
  62. Suetsugu A., Nagaki M., Aoki H., Motohashi T., Kunisada T., Moriwaki H. Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem. Biophys. Res. Commun. 2006; 351(4): 820–4. https://doi.org/10.1016/j.bbrc.2006.10.128
  63. Li Z. CD133: a stem cell biomarker and beyond. Exp. Hematol. Oncol. 2013; 2(1): 17. https://doi.org/10.1186/2162-3619-2-17
  64. Hagiwara S., Nishida N., Park A., Komeda Y., Sakurai T., Watanabe T., et al. Contribution of C1485T mutation in the HBx gene to human and murine hepatocarcinogenesis. Sci. Rep. 2017; 7(1): 10440. https://doi.org/10.1038/s41598-017-10570-0
  65. Hussain Z., Jung H.S., Ryu D.K., Ryu W.S. Genetic dissection of naturally occurring basal core promoter mutations of hepatitis B virus reveals a silent phenotype in the overlapping X gene. J. Gen. Virol. 2009; 90(Pt. 9): 2272–81. https://doi.org/10.1099/vir.0.010421-0
  66. Sánchez-Tapias J.M., Costa J., Mas A., Bruguera M., Rodés J. Influence of hepatitis B virus genotype on the long-term outcome of chronic hepatitis B in western patients. Gastroenterology. 2002; 123(6): 184–56. https://doi.org/10.1053/gast.2002.37041
  67. Kim H., Gong J.R., Lee S.A., Kim B.J. Discovery of a novel mutation (X8Del) resulting in an 8-bp deletion in the hepatitis B virus X gene associated with occult infection in Korean vaccinated individuals. PLoS One. 2015; 10(10): e0139551. https://doi.org/10.1371/journal.pone.0139551
  68. Li W., Goto K., Matsubara Y., Ito S., Muroyama R., Li Q., et al. The characteristic changes in hepatitis B virus X region for hepatocellular carcinoma: a comprehensive analysis based on global data. PLoS One. 2015; 10(5): e0125555. https://doi.org/10.1371/journal.pone.0125555
  69. Kurbanov F., Tanaka Y., Fujiwara K., Sugauchi F., Mbanya D., Zekeng L., et al. A new subtype (subgenotype) Ac (A3) of hepatitis B virus and recombination between genotypes A and E in Cameroon. J. Gen. Virol. 2005; 86(Pt. 7): 2047–56. https://doi.org/10.1099/vir.0.80922-0
  70. Wungu C.D.K., Amin M., Ruslan S.E.N., Purwono P.B., Kholili U., Maimunah U., et al. Association between host TNF-α, TGF-β1, p53 polymorphisms, HBV X gene mutation, HBV viral load and the progression of HBV-associated chronic liver disease in Indonesian patients. Biomed. Rep. 2019; 11(4): 145–53. https://doi.org/10.3892/br.2019.1239
  71. Melegari M., Wolf S.K., Schneider R.J. Hepatitis B virus DNA replication is coordinated by core protein serine phosphorylation and HBx expression. J. Virol. 2005; 79(15): 9810–20. https://doi.org/10.1128/JVI.79.15.9810-9820.2005
  72. Prieto C., Montecinos J., Jiménez G., Riquelme C., Garrido D., Hernández S., et al. Phosphorylation of phylogenetically conserved amino acid residues confines HBx within different cell compartments of human hepatocarcinoma cells. Molecules. 2021; 26(5): 1254. https://doi.org/10.3390/molecules26051254
  73. Goto T., Kato N., Ono-Nita S.K., Yoshida H., Otsuka M., Shiratori Y., et al. Large isoform of hepatitis delta antigen activates serum response factor-associated transcription. J. Biol. Chem. 2000; 275(48): 37311-6. https://doi.org/10.1074/jbc.M002947200

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2022 Panasiuk Y.V., Vlasenko N.V., Churilova N.S., Klushkina V.V., Dubodelov D.V., Kudryavtseva E.N., Korabelnikova M.I., Rodionova Z.S., Semenenko T.A., Kuzin S.N., Akimkin V.G.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».