You're using an outdated browser. Please upgrade to a modern browser for the best experience.
HBVcccDNA: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Conner Chen and Version 1 by Christine Neuveut.

Hepatitis B virus (HBV) remains a major public health concern, with more than 250 million chronically infected people who are at high risk of developing liver diseases, including cirrhosis and hepatocellular carcinoma. Although antiviral treatments efficiently control virus replication and improve liver function, they cannot cure HBV infection. Viral persistence is due to the maintenance of the viral circular episomal DNA, called covalently closed circular DNA (cccDNA), in the nuclei of infected cells. cccDNA not only resists antiviral therapies, but also escapes innate antiviral surveillance. This viral DNA intermediate plays a central role in HBV replication, as cccDNA is the template for the transcription of all viral RNAs, including pregenomic RNA (pgRNA), which in turn feeds the formation of cccDNA through a step of reverse transcription. The establishment and/or expression of cccDNA is thus a prime target for the eradication of HBV.

  • HBV
  • HBVcccDNA
  • HBV cure
  • HBc
Please wait, diff process is still running!

References

  1. Trepo, C.; Chan, H.L.; Lok, A. Hepatitis B virus infection. Lancet 2014, 384, 2053–2063.
  2. Parkin, D.M.; Bray, F.I.; Devesa, S.S. Cancer burden in the year 2000. The global picture. Eur. J. Cancer 2001, 37 (Suppl. 8), S4–S66.
  3. Szmuness, W. Hepatocellular carcinoma and the hepatitis B virus: Evidence for a causal association. Prog. Med. Virol. 1978, 24, 40–69.
  4. Nassal, M. Hepatitis B viruses: Reverse transcription a different way. Virus Res. 2008, 134, 235–249.
  5. Quasdorff, M.; Protzer, U. Control of hepatitis B virus at the level of transcription. J. Viral Hepat. 2010, 17, 527–536.
  6. Turton, K.L.; Meier-Stephenson, V.; Badmalia, M.D.; Coffin, C.S.; Patel, T.R. Host Transcription Factors in Hepatitis B Virus RNA Synthesis. Viruses 2020, 12, 160.
  7. Jiang, B.; Hildt, E. Intracellular Trafficking of HBV Particles. Cells 2020, 9, 2023.
  8. Patient, R.; Hourioux, C.; Roingeard, P. Morphogenesis of hepatitis B virus and its subviral envelope particles. Cell Microbiol. 2009, 11, 1561–1570.
  9. Selzer, L.; Zlotnick, A. Assembly and Release of Hepatitis B Virus. Cold Spring Harb. Perspect. Med. 2015, 5.
  10. Ko, C.; Chakraborty, A.; Chou, W.M.; Hasreiter, J.; Wettengel, J.M.; Stadler, D.; Bester, R.; Asen, T.; Zhang, K.; Wisskirchen, K.; et al. Hepatitis B virus genome recycling and de novo secondary infection events maintain stable cccDNA levels. J. Hepatol. 2018, 69, 1231–1241.
  11. Kock, J.; Rosler, C.; Zhang, J.J.; Blum, H.E.; Nassal, M.; Thoma, C. Generation of covalently closed circular DNA of hepatitis B viruses via intracellular recycling is regulated in a virus specific manner. PLoS Pathog. 2010, 6, e1001082.
  12. Tuttleman, J.S.; Pourcel, C.; Summers, J. Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells. Cell 1986, 47, 451–460.
  13. Summers, J.; Smith, P.M.; Horwich, A.L. Hepadnavirus envelope proteins regulate covalently closed circular DNA amplification. J. Virol. 1990, 64, 2819–2824.
  14. Hu, J.; Liu, K. Complete and Incomplete Hepatitis B Virus Particles: Formation, Function, and Application. Viruses 2017, 9, 56.
  15. Hong, X.; Luckenbaugh, L.; Mendenhall, M.; Walsh, R.; Cabuang, L.; Soppe, S.; Revill, P.A.; Burdette, D.; Feierbach, B.; Delaney, W.; et al. Characterization of Hepatitis B Precore/Core-Related Antigens. J. Virol. 2021, 95.
  16. Kimura, T.; Ohno, N.; Terada, N.; Rokuhara, A.; Matsumoto, A.; Yagi, S.; Tanaka, E.; Kiyosawa, K.; Ohno, S.; Maki, N. Hepatitis B virus DNA-negative dane particles lack core protein but contain a 22-kDa precore protein without C-terminal arginine-rich domain. J. Biol. Chem. 2005, 280, 21713–21719.
  17. Luckenbaugh, L.; Kitrinos, K.M.; Delaney, W.E., 4th; Hu, J. Genome-free hepatitis B virion levels in patient sera as a potential marker to monitor response to antiviral therapy. J. Viral Hepat. 2015, 22, 561–570.
  18. Shen, S.; Xie, Z.; Cai, D.; Yu, X.; Zhang, H.; Kim, E.S.; Zhou, B.; Hou, J.; Zhang, X.; Huang, Q.; et al. Biogenesis and molecular characteristics of serum hepatitis B virus RNA. PLoS Pathog. 2020, 16, e1008945.
  19. Wang, J.; Shen, T.; Huang, X.; Kumar, G.R.; Chen, X.; Zeng, Z.; Zhang, R.; Chen, R.; Li, T.; Zhang, T.; et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound. J. Hepatol. 2016, 65, 700–710.
  20. Revill, P.; Testoni, B.; Locarnini, S.; Zoulim, F. Global strategies are required to cure and eliminate HBV infection. Nat. Rev. Gastroenterol. Hepatol. 2016, 13, 239–248.
  21. Yan, H.; Zhong, G.; Xu, G.; He, W.; Jing, Z.; Gao, Z.; Huang, Y.; Qi, Y.; Peng, B.; Wang, H.; et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife 2012, 3.
  22. Huang, H.C.; Chen, C.C.; Chang, W.C.; Tao, M.H.; Huang, C. Entry of hepatitis B virus into immortalized human primary hepatocytes by clathrin-dependent endocytosis. J. Virol. 2012, 86, 9443–9453.
  23. Macovei, A.; Radulescu, C.; Lazar, C.; Petrescu, S.; Durantel, D.; Dwek, R.A.; Zitzmann, N.; Nichita, N.B. Hepatitis B virus requires intact caveolin-1 function for productive infection in HepaRG cells. J. Virol. 2010, 84, 243–253.
  24. Herrscher, C.; Pastor, F.; Burlaud-Gaillard, J.; Dumans, A.; Seigneuret, F.; Moreau, A.; Patient, R.; Eymieux, S.; de Rocquigny, H.; Hourioux, C.; et al. Hepatitis B virus entry into HepG2-NTCP cells requires clathrin-mediated endocytosis. Cell Microbiol. 2020, 22, e13205.
  25. Umetsu, T.; Inoue, J.; Kogure, T.; Kakazu, E.; Ninomiya, M.; Iwata, T.; Takai, S.; Nakamura, T.; Sano, A.; Shimosegawa, T. Inhibitory effect of silibinin on hepatitis B virus entry. Biochem. Biophys. Rep. 2018, 14, 20–25.
  26. Iwamoto, M.; Saso, W.; Nishioka, K.; Ohashi, H.; Sugiyama, R.; Ryo, A.; Ohki, M.; Yun, J.H.; Park, S.Y.; Ohshima, T.; et al. The machinery for endocytosis of epidermal growth factor receptor coordinates the transport of incoming hepatitis B virus to the endosomal network. J. Biol. Chem. 2020, 295, 800–807.
  27. Iwamoto, M.; Saso, W.; Sugiyama, R.; Ishii, K.; Ohki, M.; Nagamori, S.; Suzuki, R.; Aizaki, H.; Ryo, A.; Yun, J.H.; et al. Epidermal growth factor receptor is a host-entry cofactor triggering hepatitis B virus internalization. Proc. Natl. Acad. Sci. USA 2019, 116, 8487–8492.
  28. Herrscher, C.; Roingeard, P.; Blanchard, E. Hepatitis B Virus Entry into Cells. Cells 2020, 9, 1486.
  29. Hatton, T.; Zhou, S.; Standring, D.N. RNA- and DNA-binding activities in hepatitis B virus capsid protein: A model for their roles in viral replication. J. Virol. 1992, 66, 5232–5241.
  30. Kock, J.; Nassal, M.; Deres, K.; Blum, H.E.; von Weizsacker, F. Hepatitis B virus nucleocapsids formed by carboxy-terminally mutated core proteins contain spliced viral genomes but lack full-size DNA. J. Virol. 2004, 78, 13812–13818.
  31. Nassal, M. The arginine-rich domain of the hepatitis B virus core protein is required for pregenome encapsidation and productive viral positive-strand DNA synthesis but not for virus assembly. J. Virol. 1992, 66, 4107–4116.
  32. Ludgate, L.; Liu, K.; Luckenbaugh, L.; Streck, N.; Eng, S.; Voitenleitner, C.; Delaney, W.E., 4th; Hu, J. Cell-Free Hepatitis B Virus Capsid Assembly Dependent on the Core Protein C-Terminal Domain and Regulated by Phosphorylation. J. Virol. 2016, 90, 5830–5844.
  33. Tan, Z.; Pionek, K.; Unchwaniwala, N.; Maguire, M.L.; Loeb, D.D.; Zlotnick, A. The interface between hepatitis B virus capsid proteins affects self-assembly, pregenomic RNA packaging, and reverse transcription. J. Virol. 2015, 89, 3275–3284.
  34. Basagoudanavar, S.H.; Perlman, D.H.; Hu, J. Regulation of hepadnavirus reverse transcription by dynamic nucleocapsid phosphorylation. J. Virol. 2007, 81, 1641–1649.
  35. de Rocquigny, H.; Rat, V.; Pastor, F.; Darlix, J.L.; Hourioux, C.; Roingeard, P. Phosphorylation of the Arginine-Rich C-Terminal Domains of the Hepatitis B Virus (HBV) Core Protein as a Fine Regulator of the Interaction between HBc and Nucleic Acid. Viruses 2020, 12, 738.
  36. Selzer, L.; Kant, R.; Wang, J.C.; Bothner, B.; Zlotnick, A. Hepatitis B Virus Core Protein Phosphorylation Sites Affect Capsid Stability and Transient Exposure of the C-terminal Domain. J. Biol. Chem. 2015, 290, 28584–28593.
  37. Su, P.Y.; Yang, C.J.; Chu, T.H.; Chang, C.H.; Chiang, C.; Tang, F.M.; Lee, C.Y.; Shih, C. HBV maintains electrostatic homeostasis by modulating negative charges from phosphoserine and encapsidated nucleic acids. Sci Rep. 2016, 6, 38959.
  38. Christie, M.; Chang, C.W.; Rona, G.; Smith, K.M.; Stewart, A.G.; Takeda, A.A.; Fontes, M.R.; Stewart, M.; Vertessy, B.G.; Forwood, J.K.; et al. Structural Biology and Regulation of Protein Import into the Nucleus. J. Mol. Biol. 2016, 428, 2060–2090.
  39. Dohner, K.; Nagel, C.H.; Sodeik, B. Viral stop-and-go along microtubules: Taking a ride with dynein and kinesins. Trends Microbiol. 2005, 13, 320–327.
  40. Funk, A.; Mhamdi, M.; Lin, L.; Will, H.; Sirma, H. Itinerary of hepatitis B viruses: Delineation of restriction points critical for infectious entry. J. Virol. 2004, 78, 8289–8300.
  41. Rabe, B.; Glebe, D.; Kann, M. Lipid-mediated introduction of hepatitis B virus capsids into nonsusceptible cells allows highly efficient replication and facilitates the study of early infection events. J. Virol. 2006, 80, 5465–5473.
  42. Osseman, Q.; Gallucci, L.; Au, S.; Cazenave, C.; Berdance, E.; Blondot, M.L.; Cassany, A.; Begu, D.; Ragues, J.; Aknin, C.; et al. The chaperone dynein LL1 mediates cytoplasmic transport of empty and mature hepatitis B virus capsids. J. Hepatol. 2018, 68, 441–448.
  43. Eckhardt, S.G.; Milich, D.R.; McLachlan, A. Hepatitis B virus core antigen has two nuclear localization sequences in the arginine-rich carboxyl terminus. J. Virol. 1991, 65, 575–582.
  44. Li, H.C.; Huang, E.Y.; Su, P.Y.; Wu, S.Y.; Yang, C.C.; Lin, Y.S.; Chang, W.C.; Shih, C. Nuclear export and import of human hepatitis B virus capsid protein and particles. PLoS Pathog. 2010, 6, e1001162.
  45. Kann, M.; Sodeik, B.; Vlachou, A.; Gerlich, W.H.; Helenius, A. Phosphorylation-dependent binding of hepatitis B virus core particles to the nuclear pore complex. J. Cell Biol. 1999, 145, 45–55.
  46. Guo, H.; Mao, R.; Block, T.M.; Guo, J.T. Production and function of the cytoplasmic deproteinized relaxed circular DNA of hepadnaviruses. J. Virol. 2010, 84, 387–396.
  47. Rabe, B.; Vlachou, A.; Pante, N.; Helenius, A.; Kann, M. Nuclear import of hepatitis B virus capsids and release of the viral genome. Proc. Natl. Acad. Sci. USA 2003, 100, 9849–9854.
  48. Chen, C.; Wang, J.C.; Zlotnick, A. A kinase chaperones hepatitis B virus capsid assembly and captures capsid dynamics in vitro. PLoS Pathog. 2011, 7, e1002388.
  49. Wang, J.C.; Dhason, M.S.; Zlotnick, A. Structural organization of pregenomic RNA and the carboxy-terminal domain of the capsid protein of hepatitis B virus. PLoS Pathog. 2012, 8, e1002919.
  50. Cui, X.; Ludgate, L.; Ning, X.; Hu, J. Maturation-associated destabilization of hepatitis B virus nucleocapsid. J. Virol. 2013, 87, 11494–11503.
  51. Dhason, M.S.; Wang, J.C.; Hagan, M.F.; Zlotnick, A. Differential assembly of Hepatitis B Virus core protein on single- and double-stranded nucleic acid suggest the dsDNA-filled core is spring-loaded. Virology 2012, 430, 20–29.
  52. Ceres, P.; Zlotnick, A. Weak protein-protein interactions are sufficient to drive assembly of hepatitis B virus capsids. Biochemistry 2002, 41, 11525–11531.
  53. Hilmer, J.K.; Zlotnick, A.; Bothner, B. Conformational equilibria and rates of localized motion within hepatitis B virus capsids. J. Mol. Biol. 2008, 375, 581–594.
  54. Luo, J.; Xi, J.; Gao, L.; Hu, J. Role of Hepatitis B virus capsid phosphorylation in nucleocapsid disassembly and covalently closed circular DNA formation. PLoS Pathog. 2020, 16, e1008459.
  55. Chen, C.; Wang, J.C.; Pierson, E.E.; Keifer, D.Z.; Delaleau, M.; Gallucci, L.; Cazenave, C.; Kann, M.; Jarrold, M.F.; Zlotnick, A. Importin beta Can Bind Hepatitis B Virus Core Protein and Empty Core-Like Particles and Induce Structural Changes. PLoS Pathog. 2016, 12, e1005802.
  56. Rabe, B.; Delaleau, M.; Bischof, A.; Foss, M.; Sominskaya, I.; Pumpens, P.; Cazenave, C.; Castroviejo, M.; Kann, M. Nuclear entry of hepatitis B virus capsids involves disintegration to protein dimers followed by nuclear reassociation to capsids. PLoS Pathog. 2009, 5, e1000563.
  57. Schmitz, A.; Schwarz, A.; Foss, M.; Zhou, L.; Rabe, B.; Hoellenriegel, J.; Stoeber, M.; Pante, N.; Kann, M. Nucleoporin 153 arrests the nuclear import of hepatitis B virus capsids in the nuclear basket. PLoS Pathog. 2010, 6, e1000741.
  58. Cui, X.; Guo, J.T.; Hu, J. Hepatitis B Virus Covalently Closed Circular DNA Formation in Immortalized Mouse Hepatocytes Associated with Nucleocapsid Destabilization. J. Virol. 2015, 89, 9021–9028.
  59. Lempp, F.A.; Mutz, P.; Lipps, C.; Wirth, D.; Bartenschlager, R.; Urban, S. Evidence that hepatitis B virus replication in mouse cells is limited by the lack of a host cell dependency factor. J. Hepatol. 2016, 64, 556–564.
  60. Duheron, V.; Nilles, N.; Pecenko, S.; Martinelli, V.; Fahrenkrog, B. Localisation of Nup153 and SENP1 to nuclear pore complexes is required for 53BP1-mediated DNA double-strand break repair. J. Cell Sci. 2017, 130, 2306–2316.
  61. Geli, V.; Lisby, M. Recombinational DNA repair is regulated by compartmentalization of DNA lesions at the nuclear pore complex. Bioessays 2015, 37, 1287–1292.
  62. Simon, M.N.; Kalousi, A.; Soutoglou, E.; Géli, V.; Dargemont, C. Nuclear Pore Complexes in DNA Repair and Telomere Maintenance. In Nuclear Pore Complexes in Genome Organization, Function and Maintenance; D′Angelo, M., Ed.; Springer: Basel, Switzerland, 2018; pp. 201–218.
  63. Lupberger, J.; Schaedler, S.; Peiran, A.; Hildt, E. Identification and characterization of a novel bipartite nuclear localization signal in the hepatitis B virus polymerase. World J. Gastroenterol. 2013, 19, 8000–8010.
  64. Verrier, E.R.; Yim, S.A.; Heydmann, L.; El Saghire, H.; Bach, C.; Turon-Lagot, V.; Mailly, L.; Durand, S.C.; Lucifora, J.; Durantel, D.; et al. Hepatitis B Virus Evasion From Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase Sensing in Human Hepatocytes. Hepatology 2018, 68, 1695–1709.
  65. Tsukuda, S.; Watashi, K. Hepatitis B virus biology and life cycle. Antivir. Res. 2020, 182, 104925.
  66. Koniger, C.; Wingert, I.; Marsmann, M.; Rosler, C.; Beck, J.; Nassal, M. Involvement of the host DNA-repair enzyme TDP2 in formation of the covalently closed circular DNA persistence reservoir of hepatitis B viruses. Proc. Natl. Acad. Sci. USA 2014, 111, E4244–E4253.
  67. Cai, D.; Yan, R.; Xu, J.Z.; Zhang, H.; Shen, S.; Mitra, B.; Marchetti, A.; Kim, E.S.; Guo, H. Characterization of the Termini of Cytoplasmic Hepatitis B Virus Deproteinated Relaxed Circular DNA. J. Virol. 2020, 95.
  68. Kock, J.; Baumert, T.F.; Delaney, W.E., 4th; Blum, H.E.; von Weizsacker, F. Inhibitory effect of adefovir and lamivudine on the initiation of hepatitis B virus infection in primary tupaia hepatocytes. Hepatology 2003, 38, 1410–1418.
  69. Long, Q.; Yan, R.; Hu, J.; Cai, D.; Mitra, B.; Kim, E.S.; Marchetti, A.; Zhang, H.; Wang, S.; Liu, Y.; et al. The role of host DNA ligases in hepadnavirus covalently closed circular DNA formation. PLoS Pathog. 2017, 13, e1006784.
  70. Qi, Y.; Gao, Z.; Xu, G.; Peng, B.; Liu, C.; Yan, H.; Yao, Q.; Sun, G.; Liu, Y.; Tang, D.; et al. DNA Polymerase kappa Is a Key Cellular Factor for the Formation of Covalently Closed Circular DNA of Hepatitis B Virus. PLoS Pathog. 2016, 12, e1005893.
  71. Lee, M.; Zhang, S.; Wang, X.; Chao, H.H.; Zhao, H.; Darzynkiewicz, Z.; Zhang, Z.; Lee, E.Y.C. Two forms of human DNA polymerase delta: Who does what and why? DNA Repair (Amst) 2019, 81, 102656.
  72. Wei, L.; Ploss, A. Core components of DNA lagging strand synthesis machinery are essential for hepatitis B virus cccDNA formation. Nat. Microbiol. 2020, 5, 715–726.
  73. Ogi, T.; Limsirichaikul, S.; Overmeer, R.M.; Volker, M.; Takenaka, K.; Cloney, R.; Nakazawa, Y.; Niimi, A.; Miki, Y.; Jaspers, N.G.; et al. Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells. Mol. Cell 2010, 37, 714–727.
  74. Ogi, T.; Lehmann, A.R. The Y-family DNA polymerase kappa (pol kappa) functions in mammalian nucleotide-excision repair. Nat. Cell Biol. 2006, 8, 640–642.
  75. Tang, L.; Sheraz, M.; McGrane, M.; Chang, J.; Guo, J.T. DNA Polymerase alpha is essential for intracellular amplification of hepatitis B virus covalently closed circular DNA. PLoS Pathog. 2019, 15, e1007742.
  76. Kitamura, K.; Que, L.; Shimadu, M.; Koura, M.; Ishihara, Y.; Wakae, K.; Nakamura, T.; Watashi, K.; Wakita, T.; Muramatsu, M. Flap endonuclease 1 is involved in cccDNA formation in the hepatitis B virus. PLoS Pathog. 2018, 14, e1007124.
  77. Sheraz, M.; Cheng, J.; Tang, L.; Chang, J.; Guo, J.T. Cellular DNA Topoisomerases Are Required for the Synthesis of Hepatitis B Virus Covalently Closed Circular DNA. J. Virol. 2019, 93.
  78. Luo, J.; Cui, X.; Gao, L.; Hu, J. Identification of an Intermediate in Hepatitis B Virus Covalently Closed Circular (CCC) DNA Formation and Sensitive and Selective CCC DNA Detection. J. Virol. 2017, 91.
  79. Wei, L.; Ploss, A. Hepatitis B virus cccDNA is formed through distinct repair processes of each strand. Nat. Commun. 2021, 12, 1591.
  80. Luo, J.; Luckenbaugh, L.; Hu, H.; Yan, Z.; Gao, L.; Hu, J. Involvement of Host ATR-CHK1 Pathway in Hepatitis B Virus Covalently Closed Circular DNA Formation. mBio 2020, 11.
  81. Fortini, P.; Dogliotti, E. Mechanisms of dealing with DNA damage in terminally differentiated cells. Mutat. Res. 2010, 685, 38–44.
  82. Simonatto, M.; Latella, L.; Puri, P.L. DNA damage and cellular differentiation: More questions than responses. J. Cell Physiol. 2007, 213, 642–648.
  83. Gillman, R.; Lopes Floro, K.; Wankell, M.; Hebbard, L. The role of DNA damage and repair in liver cancer. Biochim. Biophys. Acta Rev. Cancer 2021, 1875, 188493.
  84. Nickoloff, J.A.; Jones, D.; Lee, S.H.; Williamson, E.A.; Hromas, R. Drugging the Cancers Addicted to DNA Repair. J. Natl. Cancer Inst. 2017, 109.
  85. Bock, C.T.; Schranz, P.; Schroder, C.H.; Zentgraf, H. Hepatitis B virus genome is organized into nucleosomes in the nucleus of the infected cell. Virus Genes 1994, 8, 215–229.
  86. Bock, C.T.; Schwinn, S.; Locarnini, S.; Fyfe, J.; Manns, M.P.; Trautwein, C.; Zentgraf, H. Structural organization of the hepatitis B virus minichromosome. J. Mol. Biol. 2001, 307, 183–196.
  87. Shi, L.; Li, S.; Shen, F.; Li, H.; Qian, S.; Lee, D.H.; Wu, J.Z.; Yang, W. Characterization of nucleosome positioning in hepadnaviral covalently closed circular DNA minichromosomes. J. Virol. 2012, 86, 10059–10069.
  88. Tropberger, P.; Mercier, A.; Robinson, M.; Zhong, W.; Ganem, D.E.; Holdorf, M. Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual chromatin organization amenable to epigenetic manipulation. Proc. Natl. Acad. Sci. USA 2015, 112, E5715–E5724.
  89. Belloni, L.; Pollicino, T.; De Nicola, F.; Guerrieri, F.; Raffa, G.; Fanciulli, M.; Raimondo, G.; Levrero, M. Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function. Proc. Natl. Acad. Sci. USA 2009, 106, 19975–19979.
  90. Pollicino, T.; Belloni, L.; Raffa, G.; Pediconi, N.; Squadrito, G.; Raimondo, G.; Levrero, M. Hepatitis B virus replication is regulated by the acetylation status of hepatitis B virus cccDNA-bound H3 and H4 histones. Gastroenterology 2006, 130, 823–837.
  91. Riviere, L.; Gerossier, L.; Ducroux, A.; Dion, S.; Deng, Q.; Michel, M.L.; Buendia, M.A.; Hantz, O.; Neuveut, C. HBx relieves chromatin-mediated transcriptional repression of hepatitis B viral cccDNA involving SETDB1 histone methyltransferase. J. Hepatol. 2015, 63, 1093–1102.
  92. Flecken, T.; Meier, M.A.; Skewes-Cox, P.; Barkan, D.T.; Heim, M.H.; Wieland, S.F.; Holdorf, M.M. Mapping the Heterogeneity of Histone Modifications on Hepatitis B Virus DNA Using Liver Needle Biopsies Obtained from Chronically Infected Patients. J. Virol. 2019, 93.
  93. Alvarez-Astudillo, F.; Garrido, D.; Varas-Godoy, M.; Gutierrez, J.L.; Villanueva, R.A.; Loyola, A. The histone variant H3.3 regulates the transcription of the hepatitis B virus. Ann. Hepatol. 2021, 21, 100261.
  94. Wang, Z.; Wang, W.; Wang, L. Epigenetic regulation of covalently closed circular DNA minichromosome in hepatitis B virus infection. Biophys. Rep. 2020, 6, 115–126.
  95. Tu, T.; Budzinska, M.A.; Shackel, N.A.; Urban, S. HBV DNA Integration: Molecular Mechanisms and Clinical Implications. Viruses 2017, 9, 75.
  96. Yang, W.; Summers, J. Illegitimate replication of linear hepadnavirus DNA through nonhomologous recombination. J. Virol. 1995, 69, 4029–4036.
  97. Zhao, L.H.; Liu, X.; Yan, H.X.; Li, W.Y.; Zeng, X.; Yang, Y.; Zhao, J.; Liu, S.P.; Zhuang, X.H.; Lin, C.; et al. Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma. Nat. Commun. 2016, 7, 12992.
  98. Buendia, M.A.; Neuveut, C. Hepatocellular carcinoma. Cold Spring Harb. Perspect. Med. 2015, 5, a021444.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Academic Video Service
Feedback