Review

Mutations and methods of analysis of mutations in Hepatitis B virus

  • Received: 29 July 2020 Accepted: 23 October 2020 Published: 27 October 2020
  • Immunization programmes against hepatitis-B are being carried out since more than three decades but still HBV is a major public health problem. Hepatitis B virus (HBV) genome consists of circular and partial double stranded DNA. Due to partial double stranded DNA, it uses an RNA intermediate during replication. This replicative strategy of HBV and lack of polymerase proofreading activity give rise to error occurrences comparable to retroviruses. The low fidelity of polymerase, overlapping reading frames and high replication rate produces many non-identical variants at every cycle of replication. Therefore, HBV spreads with mutations and variations. The mutations have been reported both in non-structural as well as structural genes of HBV genome. Recent advances in molecular biology have made easier to analyse these mutations. Hepatitis B antiviral therapy and immunization are all influenced by genetic variability. The analysis and understanding of these mutations are important for therapy against hepatitis B and updating of diagnostic tools. The present review discusses about mutations occurring in whole HBV genome. The mutation occurring both in structural and non-structural genes and non-coding regions have been described in details. It is much more informative because most of literature available, covers only individual gene or DNA regions of HBV.

    Citation: Manoj Kumar Rajput. Mutations and methods of analysis of mutations in Hepatitis B virus[J]. AIMS Microbiology, 2020, 6(4): 401-421. doi: 10.3934/microbiol.2020024

    Related Papers:

  • Immunization programmes against hepatitis-B are being carried out since more than three decades but still HBV is a major public health problem. Hepatitis B virus (HBV) genome consists of circular and partial double stranded DNA. Due to partial double stranded DNA, it uses an RNA intermediate during replication. This replicative strategy of HBV and lack of polymerase proofreading activity give rise to error occurrences comparable to retroviruses. The low fidelity of polymerase, overlapping reading frames and high replication rate produces many non-identical variants at every cycle of replication. Therefore, HBV spreads with mutations and variations. The mutations have been reported both in non-structural as well as structural genes of HBV genome. Recent advances in molecular biology have made easier to analyse these mutations. Hepatitis B antiviral therapy and immunization are all influenced by genetic variability. The analysis and understanding of these mutations are important for therapy against hepatitis B and updating of diagnostic tools. The present review discusses about mutations occurring in whole HBV genome. The mutation occurring both in structural and non-structural genes and non-coding regions have been described in details. It is much more informative because most of literature available, covers only individual gene or DNA regions of HBV.


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    The author declares no conflicts of interest in this paper.

    [1] Dienstag JL (2008) Hepatitis B virus infection. N Engl J Med 359: 1486-500. doi: 10.1056/NEJMra0801644
    [2] Seeger C, Mason WS (2000) Hepatitis B virus biology. Microbiol Mol Biol Rev 64: 51-68. doi: 10.1128/MMBR.64.1.51-68.2000
    [3] Orito E, Mizokami M, Ina Y (1989) Host-independent evolution and a genetic classification of the hepadnavirus family based on nucleotide sequences. Proc Natl Acad Sci USA 86: 7059-7062. doi: 10.1073/pnas.86.18.7059
    [4] Gunther S, Sommer G, Plikat U, et al. (1997) Naturally occurring hepatitis B virus genomes bearing the hallmarks of retroviral G-->A hypermutation. Virology 235: 104-108. doi: 10.1006/viro.1997.8676
    [5] Henningfeld KA, Hecht SM (1995) A model for topoisomerase I-mediated insertions and deletions with duplex DNA substrates containing branches, nicks, and gaps. Biochemistry 34: 6120-6129. doi: 10.1021/bi00018a015
    [6] Liao H, Li X, Liu Y, et al. (2017) Intergenotype recombinant analysis of full-length hepatitis B virus genomes from 516 Chinese patients with different illness categories. J Med Virol 89: 139-145. doi: 10.1002/jmv.24609
    [7] Chavan YG, Pawar SR, Wani M, et al. (2017) Hepatitis B virus DNA polymerase gene polymorphism based prediction of genotypes in chronic HBV patients from Western India. Afr Health Sci 17: 762-772. doi: 10.4314/ahs.v17i3.19
    [8] Wang X, Xu L, Chen Y, et al. (2017) Integrating nested PCR with high-throughput sequencing to characterize mutations of HBV genome in low viral load samples. Medicine (Baltimore) 96: e7588. doi: 10.1097/MD.0000000000007588
    [9] Lindh M, Andersson AS, Gusdal A (1997) Genotypes, nt 1858 variants, and geographic origin of hepatitis B virus--large-scale analysis using a new genotyping method. J Infect Dis 175: 1285-1293. doi: 10.1086/516458
    [10] Wang YZ, Zhu Z, Zhang HY, et al. (2014) Detection of hepatitis B virus A1762T/G1764A mutant by amplification refractory mutations ystem. Braz J Infect Dis 18: 261-265. doi: 10.1016/j.bjid.2013.09.005
    [11] Hua R, Tanaka Y, Fukai K, et al. (2008) Rapid detection of the hepatitis B virus YMDD mutant using TaqMan-minor groove binder probes. Clin Chim Acta 395: 151-154. doi: 10.1016/j.cca.2008.06.013
    [12] Hardie DR, Kannemeyer J, Stannard LM (1996) DNA single strand conformation polymorphism identifies five defined strains of hepatitis B virus (HBV) during an outbreak of HBV infection in an oncology unit. J Med Virol 49: 49-54. doi: 10.1002/(SICI)1096-9071(199605)49:1<49::AID-JMV8>3.0.CO;2-K
    [13] Gunther S, Li BC, Miska S, et al. (1995) A novel method for efficient amplification of whole hepatitis B virus genomes permits rapid functional analysis and reveals deletion mutants in immunosuppressed patients. J Virol 69: 5437-5444. doi: 10.1128/JVI.69.9.5437-5444.1995
    [14] Xiao T, Zhou W (2020) The third generation sequencing: the advanced approach to genetic diseases. Translational pediatrics 9: 163-173. doi: 10.21037/tp.2020.03.06
    [15] Kramvis A, Kew MC (1998) Structure and function of the encapsidationsignal of hepadnaviridae. J Viral Hepat 5: 357-367. doi: 10.1046/j.1365-2893.1998.00124.x
    [16] Jammeh S, Tavner F, Watson R, et al. (2008) Effect of basal core promoter and pre-core mutations on hepatitis B virus replication. J Gen Virol 89: 901-909. doi: 10.1099/vir.0.83468-0
    [17] Buckwold VE, Xu Z, Yen TS, et al. (1997) Effects of a frequent double-nucleotide basal core promoter mutation and its putative single-nucleotide precursor mutations on hepatitis B virus gene expression and replication. J Gen Virol 78: 2055-2065. doi: 10.1099/0022-1317-78-8-2055
    [18] Gunther S, Paulij W, Meisel H, et al. (1998) Analysis of hepatitis B virus populations in an interferon-alpha-treated patient reveals predominant mutations in the C-gene and changing e-antigenicity. Virology 244: 146-160. doi: 10.1006/viro.1998.9079
    [19] Gunther S, Piwon N, Iwanska A, et al. (1996) Type, prevalence, and significance of core promoter/enhancer II mutations in hepatitis B viruses from immunosuppressed patients with severe liver disease. J Virol 70: 8318-8331. doi: 10.1128/JVI.70.12.8318-8331.1996
    [20] Preisler-Adams S, Schlayer HJ, Peters T, et al. (1993) Sequence analysis of hepatitis B virus DNA in immunologically negative infection. Arch Virol 133: 385-396. doi: 10.1007/BF01313777
    [21] Kim JH, Kang S, Kim J, et al. (2003) Hepatitis B virus core protein stimulates the proteasome-mediated degradation of viral X protein. J Virol 77: 7166-7173. doi: 10.1128/JVI.77.13.7166-7173.2003
    [22] Uchida T, Gotoh K, Shikata T (1995) Complete nucleotide sequences and the characteristics of two hepatitis B virus mutants causing serologically negative acute or chronic hepatitis B. J Med Virol 45: 247-252. doi: 10.1002/jmv.1890450303
    [23] Feitelson MA, Duan LX, Guo J, et al. (1995) Precore and X region mutants in hepatitis B virus infections among renal dialysis patients. J Viral Hepat 2: 19-31. doi: 10.1111/j.1365-2893.1995.tb00068.x
    [24] Inoue J, Ueno Y, Wakui Y, et al. (2011) Enhanced replication of hepatitis B virus with frame shift in the precoreregion found in fulminant hepatitis patients. J Infect Dis 204: 1017-1025. doi: 10.1093/infdis/jir485
    [25] Hai H, Tamori A, Kawada N (2014) Role of hepatitis B virus DNA integration in human hepatocarcinogenesis. World J Gastroenterol 20: 6236-6243. doi: 10.3748/wjg.v20.i20.6236
    [26] Bouchard MJ, Schneider RJ (2004) The enigmatic X gene of hepatitis B virus. J Virol 78: 12725-12734. doi: 10.1128/JVI.78.23.12725-12734.2004
    [27] Kramvis A, Kostaki EG, Hatzakis A, et al. (2018) Immunomodulatory function of HBeAg related to short-sighted evolution, transmissibility, and clinical manifestation of Hepatitis B virus. Front Microbiol 9: 2521. doi: 10.3389/fmicb.2018.02521
    [28] Milich DR, McLachlan A, Moriarty A, et al. (1987) Immune response to hepatitis B virus core antigen (HBcAg): localization of T cell recognition sites within HBcAg/HBeAg. J Immunol 139: 1223-1231.
    [29] Quarleri J (2014) Core promoter: A critical region where the hepatitis B virus makes decisions. World J Gastroenterol 20: 425-435. doi: 10.3748/wjg.v20.i2.425
    [30] Lin CL, Liao LY, Liu CJ, et al. (2002) Hepatitis B genotypes and precore/basal core promoter mutants in HBeAg-negative chronic hepatitis B. J Gastroenterol 37: 283-287. doi: 10.1007/s005350200036
    [31] Laskus T, Rakela J, Persing DH (1994) The stem-loop structure of the cis-encapsidation signal is highly conserved in naturally occurring hepatitis B virus variants. Virology 200: 809-812. doi: 10.1006/viro.1994.1247
    [32] Tong SP, Li JS, Vitvitski L, et al. (1992) Replication capacities of natural and artificial precore stop codon mutants of hepatitis B virus: relevance of pregenome encapsidation signal. Virology 191: 237-245. doi: 10.1016/0042-6822(92)90185-R
    [33] Tong SP, Li JS, Vitvitski L, et al. (1993) Evidence for a base-paired region of hepatitis B virus pregenome encapsidation signal which influences the patterns of precore mutations abolishing HBe protein expression. J Virol 67: 5651-5655. doi: 10.1128/JVI.67.9.5651-5655.1993
    [34] Guo Y, Hou J, Luo K, et al. (2001) Genetic mutations of precoreregion of hepatitis B virus in hepatitis B e antigen-negative patients with fulminant hepatitis B and translation of precore variants in vitro. Zhonghua Gan Zang Bing Za Zhi 9: 42-44.
    [35] Gunther S, Meisel H, Reip A, et al. (1992) Frequent and rapid emergence of mutated pre-C sequences in HBV from e-antigen positive carriers who seroconvert to anti-HBe during interferon treatment. Virology 187: 271-279. doi: 10.1016/0042-6822(92)90315-G
    [36] Ingman M, Lindqvist B, Kidd-Ljunggren K (2006) Novel mutation in Hepatitis B virus preventing HBeAg production and resembling primate strains. J Gen Virol 87: 307-310. doi: 10.1099/vir.0.81562-0
    [37] Laskus T, Rakela J, Persing DH (1995) Nucleotide sequence analysis of precore and proximal core regions in patients with chronic hepatitis B treated with interferon. Dig Dis Sci 40: 1-7. doi: 10.1007/BF02063933
    [38] Marinos G, Torre F, Gunther S, et al. (1996) Hepatitis B virus variants with core gene deletions in the evolution of chronic hepatitis B infection. Gastroenterology 111: 183-192. doi: 10.1053/gast.1996.v111.pm8698197
    [39] Santantonio T, Jung MC, Schneider R, et al. (1991) Selection for a pre-C stop codon mutation in a hepatitis B virus variant with a pre-C initiation codon mutation during interferon treatment. J Hepatol 13: 368-371. doi: 10.1016/0168-8278(91)90083-N
    [40] Grandjacques C, Pradat P, Stuyver L, et al. (2000) Rapid detection of genotypes and mutations in the pre-core promoter and the pre-core region of hepatitis B virus genome: correlation with viral persistence and disease severity. J Hepatol 33: 430-439. doi: 10.1016/S0168-8278(00)80279-2
    [41] Nakahori S, Yokosuka O, Ehata T, et al. (1995) Detection of hepatitis B virus precore stop codon mutants by selective amplification method: frequent detection of precore mutants in hepatitis B e antigen positive healthy carriers. J Gastroenterol Hepatol 10: 419-425. doi: 10.1111/j.1440-1746.1995.tb01594.x
    [42] Zhong S, Chan JY, Yeo W, et al. (2000) Frequent integration of precore/core mutants of hepatitis B virus in human hepatocellular carcinoma tissues. J Viral Hepat 7: 115-123. doi: 10.1046/j.1365-2893.2000.00209.x
    [43] Naumann U, Protzer-Knolle U, Berg T, et al. (1997) A pretransplant infection with precore mutants of hepatitis B virus does not influence the outcome of orthotopic liver transplantation in patients on high dose anti-hepatitis B virus surface antigen immunoprophylaxis. Hepatology 26: 478-484. doi: 10.1002/hep.510260232
    [44] Salfeld J, Pfaff E, Noah M, et al. (1989) Antigenic determinants and functional domains in core antigen and e antigen from hepatitis B virus. J Virol 63: 798-808. doi: 10.1128/JVI.63.2.798-808.1989
    [45] Sallberg M, Ruden U, Wahren B, et al. (2012) Human and murine B-cells recognize the HBeAg/beta (or HBe2) epitope as a linear determinant. Mol Immunol 28: 719-726. doi: 10.1016/0161-5890(91)90114-Y
    [46] Konig S, Beterams G, Nassal M (1998) Mapping of homologous interaction sites in the hepatitis B virus core protein. J Virol 72: 4997-5005. doi: 10.1128/JVI.72.6.4997-5005.1998
    [47] Metzger K, Bringas R (1998) Proline-138 is essential for the assembly of hepatitis B virus core protein. J Gen Virol 79: 587-590. doi: 10.1099/0022-1317-79-3-587
    [48] Zlotnick A, Cheng N, Stahl SJ, et al. (1997) Localization of the C-terminus of the assembly domain of hepatitis B virus capsid protein: implications for morphogenesis and organization of encapsidated RNA. Proc Natl Acad Sci USA 94: 9556-9561. doi: 10.1073/pnas.94.18.9556
    [49] Ehata T, Omata M, Chuang WL, et al. (1993) Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis. J Clin Invest 91: 1206-1213. doi: 10.1172/JCI116281
    [50] Bertoletti A, Costanzo A, Chisari FV, et al. (1994) Cytotoxic T lymphocyte response to a wild type hepatitis B virus epitope in patients chronically infected by variant viruses carrying substitutions within the epitope. J Exp Med 180: 933-943. doi: 10.1084/jem.180.3.933
    [51] Rehermann B, Fowler P, Sidney J, et al. (1995) The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis. J Exp Med 181: 1047-1058. doi: 10.1084/jem.181.3.1047
    [52] Hosono S, Tai PC, Wang W, et al. (1995) Core antigen mutations of human hepatitis B virus in hepatomas accumulate in MHC class II-restricted T cell epitopes. Virology 212: 151-162. doi: 10.1006/viro.1995.1463
    [53] Minami M, Poussin K, Kew M, et al. (1996) Precore/core mutations of hepatitis B virus in hepatocellular carcinomas developed on non-cirrhotic livers. Gastroenterology 111: 691-700. doi: 10.1053/gast.1996.v111.pm8780574
    [54] Yuan TT, Sahu GK, Whitehead WE, et al. (1999) The mechanism of an immature secretion phenotype of a highly frequent naturally occurring missense mutation at codon 97 of human hepatitis B virus core antigen. J Virol 73: 5731-5740. doi: 10.1128/JVI.73.7.5731-5740.1999
    [55] Schories M, Peters T, Rasenack J (2000) Isolation, characterization and biological significance of hepatitis B virus mutants from serum of a patient with immunologically negative HBV infection. J Hepatol 33: 799-811. doi: 10.1016/S0168-8278(00)80313-X
    [56] Alexopoulou A, Karayiannis P, Hadziyannis SJ, et al. (1997) Emergence and selection of HBV variants in an anti-HBe positive patient persistently infected with quasi-species. J Hepatol 26: 748-753. doi: 10.1016/S0168-8278(97)80238-3
    [57] Kreutz C (2002) Molecular, immunological and clinical properties of mutated hepatitis B viruses. J Cell Mol Med 6: 113-143. doi: 10.1111/j.1582-4934.2002.tb00317.x
    [58] Okamoto H, Wang Y, Tanaka T, et al. (1993) Machida A, Miyakawa Y, Mayumi M. Trans-complementation among naturally occurring deletion mutants of hepatitis B virus and integrated viral DNA for the production of viral particles with mutant genomes in hepatoma cell lines. J Gen Virol 74: 407-414. doi: 10.1099/0022-1317-74-3-407
    [59] Peiffer KH, Akhras S, Himmelsbach K, et al. (2015) Intracellular accumulation of subviral HBsAg particles and diminished Nrf2 activation in HBV genotype G expressing cells lead to an increased ROI level. J Hepatol 62: 791-798. doi: 10.1016/j.jhep.2014.11.028
    [60] Delfini C, Colloca S, Taliani G, et al. (1989) Clearance of hepatitis B virus DNA and pre-S surface antigens in patients with markers of acute viral replication. J Med Virol 28: 169-175. doi: 10.1002/jmv.1890280312
    [61] Melegari M, Scaglioni PP, Wands JR (1997) The small envelope protein is required for secretion of a naturally occurring hepatitis B virus mutant with pre-S1 deleted. J Virol 71: 5449-5454. doi: 10.1128/JVI.71.7.5449-5454.1997
    [62] Chua PK, Wang RY, Lin MH, et al. (2005) Reduced secretion of virions and hepatitis B virus (HBV) surface antigen of a naturally occurring HBV variant correlates with the accumulation of the small S envelope protein in the endoplasmic reticulum and Golgi apparatus. J Virol 79: 13483-13496. doi: 10.1128/JVI.79.21.13483-13496.2005
    [63] Gao ZY, Li T, Wang J, et al. (2007) Mutations in preS genes of genotype C hepatitis B virus in patients with chronic hepatitis B and hepatocellular carcinoma. J Gastroenterol 42: 761-768. doi: 10.1007/s00535-007-2085-1
    [64] Yamamoto K, Horikita M, Tsuda F, et al. (1994) Naturally occurring escape mutants of hepatitis B virus with various mutations in the S gene in carriers seropositive for antibody to hepatitis B surface antigen. J Virol 68: 2671-2676. doi: 10.1128/JVI.68.4.2671-2676.1994
    [65] Li D, He W, Liu X (2017) A potent human neutralizing antibody Fc-dependently reduces established HBV infections. Elife 6: e26738. doi: 10.7554/eLife.26738
    [66] Fernholz D, Galle PR, Stemler M, et al. (1993) Infectious hepatitis B virus variant defective in pre-S2 protein expression in a chronic carrier. Virology 194: 137-148. doi: 10.1006/viro.1993.1243
    [67] Raney AK, McLachlan A (1997) Characterization of the hepatitis B virus major surface antigen promoter hepatocyte nuclear factor 3 binding site. J Gen Virol 78: 3029-3038. doi: 10.1099/0022-1317-78-11-3029
    [68] Horikita M, Itoh S, Yamamoto K, et al. (1994) Differences in the entire nucleotide sequence between hepatitis B virus genomes from carriers positive for antibody to hepatitis B e antigen with and without active disease. J Med Virol 44: 96-103. doi: 10.1002/jmv.1890440118
    [69] Gerner PR, Friedt M, Oettinger R, et al. (1998) The hepatitis B virus seroconversion to anti-HBe is frequently associated with HBV genotype changes and selection of preS2-defective particles in chronically infected children. Virology 245: 163-172. doi: 10.1006/viro.1998.9126
    [70] Lu CC, Yen TS (1996) Activation of the hepatitis B virus S promoter by transcription factor NF-Y via a CCAAT element. Virology 225: 387-394. doi: 10.1006/viro.1996.0613
    [71] Chen BF, Liu CJ, Jow GM, et al. (2006) High prevalence and mapping of pre-S deletion in hepatitis B virus carriers with progressive liver diseases. Gastroenterology 130: 1153-1168. doi: 10.1053/j.gastro.2006.01.011
    [72] Hildt E, Saher G, Bruss V, et al. (1996) The hepatitis B virus large surface protein (LHBs) is a transcriptional activator. Virology 225: 235-239. doi: 10.1006/viro.1996.0594
    [73] Bruss V (1997) A short linear sequence in the pre-S domain of the large hepatitis B virus envelope protein required for virion formation. J Virol 71: 9350-9357. doi: 10.1128/JVI.71.12.9350-9357.1997
    [74] Lenhoff RJ, Summers J (1994) Coordinate regulation of replication and virus assembly by the large envelope protein of an avian hepadnavirus. J Virol 68: 4565-4571. doi: 10.1128/JVI.68.7.4565-4571.1994
    [75] Nakajima E, Minami M, Ochiya T, et al. (1994) PreS1 deleted variants of hepatitis B virus in patients with chronic hepatitis. J Hepatol 20: 329-335. doi: 10.1016/S0168-8278(94)80003-0
    [76] Santantonio T, Jung MC, Schneider R, et al. (1992) Hepatitis B virus genomes that cannot synthesize pre-S2 proteins occur frequently and as dominant virus populations in chronic carriers in Italy. Virology 188: 948-952. doi: 10.1016/0042-6822(92)90559-8
    [77] Hur GM, Lee YI, Suh DJ, et al. (1996) Gradual accumulation of mutations in precore core region of HBV in patients with chronic active hepatitis: implications of clustering changes in a small region of the HBV core region. J Med Virol 48: 38-46. doi: 10.1002/(SICI)1096-9071(199601)48:1<38::AID-JMV6>3.0.CO;2-M
    [78] Kohno H, Inoue T, Tsuda F, et al. (1996) Mutations in the envelope gene of hepatitis B virus variants co-occurring with antibody to surface antigen in sera from patients with chronic hepatitis B. J Gen Virol 77: 1825-1831. doi: 10.1099/0022-1317-77-8-1825
    [79] Riedl P, El-Kholy S, Reimann J, et al. (2002) Priming biologically active antibody responses against an isolated, conformational viral epitope by DNA vaccination. J Immunol 169: 1251-1260. doi: 10.4049/jimmunol.169.3.1251
    [80] Salpini R, Colagrossi L, Bellocchi MC (2015) Hepatitis B surface antigen genetic elements critical for immune escape correlate with hepatitis B virus reactivation upon immunosuppression. Hepatology 61: 823-833. doi: 10.1002/hep.27604
    [81] Rodriguez-Frias F, Buti M, Jardi R, et al. (1999) Genetic alterations in the S gene of hepatitis B virus in patients with acute hepatitis B, chronic hepatitis B and hepatitis B liver cirrhosis before and after liver transplantation. Liver 19: 177-182. doi: 10.1111/j.1478-3231.1999.tb00032.x
    [82] Ogata N, Zanetti AR, Yu M, et al. (1997) Infectivity and pathogenicity in chimpanzees of a surface gene mutant of hepatitis B virus that emerged in a vaccinated infant. J Infect Dis 175: 511-523. doi: 10.1093/infdis/175.3.511
    [83] Ngui SL, Andrews NJ, Underhill GS, et al. (1998) Failed postnatal immunoprophylaxis for hepatitis B: characteristics of maternal hepatitis B virus as risk factors. Clin Infect Dis 27: 100-106. doi: 10.1086/514610
    [84] Lee YI, Hong YB, Kim Y, et al. (1997) RNaseH activity of human hepatitis B virus polymerase expressed in Escherichia coli. Biochem Biophys Res Commun 233: 401-407. doi: 10.1006/bbrc.1997.6467
    [85] Ghany MG, Ayola B, Villamil FG, et al. (1998) Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis. Hepatology 27: 213-222. doi: 10.1002/hep.510270133
    [86] Carman WF, Trautwein C, van Deursen FJ, et al. (1996) Hepatitis B virus envelope variation after transplantation with and without hepatitis B immune globulin prophylaxis. Hepatology 24: 489-493. doi: 10.1002/hep.510240304
    [87] Tai PC, Banik D, Lin GI, et al. (1997) Novel and frequent mutations of hepatitis B virus coincide with a major histocompatibility complex class I-restricted T-cell epitope of the surface antigen. J Virol 71: 4852-4856. doi: 10.1128/JVI.71.6.4852-4856.1997
    [88] Zeinab Nabil Ahmed Said (2011) An overview of occult hepatitis B virus infection. World J Gastroenterol 17: 1927-1938. doi: 10.3748/wjg.v17.i15.1927
    [89] Carman WF (1997) The clinical significance of surface antigen variants of hepatitis B virus. J Viral Hepat 4: 11-20. doi: 10.1111/j.1365-2893.1997.tb00155.x
    [90] Zhang YY, Nordenfelt E, Hansson BG (1996) Increasing heterogeneity of the ‘a’ determinant of HBsAg found in the presumed late phase of chronic hepatitis B virus infection. Scand J Infect Dis 28: 9-15. doi: 10.3109/00365549609027142
    [91] Grethe S, Monazahian M, Bohme I, et al. (1998) Characterization of unusual escape variants of hepatitis B virus isolated from a hepatitis B surface antigen-negative subject. J Virol 72: 7692-7696. doi: 10.1128/JVI.72.9.7692-7696.1998
    [92] Cooreman MP, Leroux-Roels G, Paulij WP (2001) Vaccine and hepatitis B immune globulin-induced escape mutations of hepatitis B virus surface antigen. J Biomed Sci 8: 237-247. doi: 10.1007/BF02256597
    [93] Protzer-Knolle U, Naumann U, Bartenschlager R, et al. (1998) Hepatitis B virus with antigenically altered hepatitis B surface antigen is selected by high-dose hepatitis B immune globulin after liver transplantation. Hepatology 27: 254-263. doi: 10.1002/hep.510270138
    [94] Chen Y, Qian F, Yuan Q, et al. (2011) Mutations in hepatitis B virus DNA from patients with coexisting HBsAg and anti-HBs. J Clin Virol 52: 198-203. doi: 10.1016/j.jcv.2011.07.011
    [95] Allen MI, Deslauriers M, Andrews CW, et al. (1998) Identification and characterization of mutations in hepatitis B virus resistant to lamivudine. Hepatology 27: 1670-1677. doi: 10.1002/hep.510270628
    [96] Ono-Nita SK, Kato N, Shiratori Y, et al. (1999) Susceptibility of lamivudine-resistant hepatitis B virus to other reverse transcriptase inhibitors. J Clin Investig 103: 1635-1640. doi: 10.1172/JCI5882
    [97] Melegari M, Scaglioni PP, Wands JR (1998) Hepatitis B virus mutants associated with 3TC and famciclovir administration are replication defective. Hepatology 27: 628-633. doi: 10.1002/hep.510270243
    [98] Ladner SK, Miller TJ, Otto MJ, et al. (1998) The hepatitis B virus M539V polymerase variation responsible for 3TC resistance also confers cross-resistance to other nucleoside analogues. Antivir Chem Chemother 9: 65-72.
    [99] Stuyver LJ, Lostia S, Adams M, et al. (2002) Antiviral activities and cellular toxicities of modified 2′,3′-dideoxy-2′,3′-didehydrocytidine analogues. Antimicrob Agents Chemother 46: 3854-3860. doi: 10.1128/AAC.46.12.3854-3860.2002
    [100] Bartholomeusz A, Locarnini SA (2006) Antiviral drug resistance: clinical consequences and molecular aspects. Semin Liver Dis 26: 162-170. doi: 10.1055/s-2006-939758
    [101] Oon CJ, Chen WN, Lim N, et al. (1999) Hepatitis B virus variants with lamivudine-related mutations in the DNA polymerase and the ‘a’ epitope of the surface antigen are sensitive to ganciclovir. Antiviral Res 41: 113-118. doi: 10.1016/S0166-3542(99)00007-8
    [102] de Man RA, Bartholomeusz AI, Niesters HG, et al. (1998) The sequential occurrence of viral mutations in a liver transplant recipient re-infected with hepatitis B: hepatitis B immune globulin escape, famciclovir non-response, followed by lamivudine resistance resulting in graft loss. J Hepatol 29: 669-675. doi: 10.1016/S0168-8278(98)80164-5
    [103] Pillay D (1998) Emergence and control of resistance to antiviral drugs in resistance in herpes viruses, hepatitis B virus, and HIV. Commun Dis Public Health 1: 5-13.
    [104] Chin R, Shaw T, Torresi J, et al. (2001) In vitro susceptibilities of wild-type or drug-resistant hepatitis B virus to (-)-beta-D-2,6-diaminopurinedioxolane and 2′-fluoro-5-methyl-beta-L-arabinofuranosyluracil. Antimicrob Agents Chemother 45: 2495-2501. doi: 10.1128/AAC.45.9.2495-2501.2001
    [105] Honkoop P, Niesters HG, de Man RA, et al. (1997) Lamivudine resistance in immunocompetent chronic hepatitis B. Incidence and patterns. J Hepatol 26: 1393-1395. doi: 10.1016/S0168-8278(97)80476-X
    [106] Whalley SA, Brown D, Webster GJ, et al. (2004) Evolution of hepatitis B virus during primary infection in humans: transient generation of cytotoxic T-cell mutants. Gastroenterology 127: 1131-1138. doi: 10.1053/j.gastro.2004.07.004
    [107] Mutimer D, Pillay D, Cook P, et al. (2000) Selection of multi resistant hepatitis B virus during sequential nucleoside-analogue therapy. J Infect Dis 181: 713-716. doi: 10.1086/315238
    [108] Kreutz C (2002) Molecular, immunological and clinical properties of mutated hepatitis B viruses. J Cell Mol Med 6: 113-143. doi: 10.1111/j.1582-4934.2002.tb00317.x
    [109] Tu T, Budzinska MA, Shackel NA, et al. (2017) HBV DNA integration: molecular mechanisms and clinical implications. Viruses 9: 75. doi: 10.3390/v9040075
    [110] Sommer G, Gunther S, Sterneck M, et al. (1997) A new class of defective hepatitis B virus genomes with an internalpoly(dA) sequence. Virology 239: 402-412. doi: 10.1006/viro.1997.8898
    [111] Chen PJ, Chen CR, Sung JL, et al. (1989) Identification of a doubly spliced viral transcript joining the separated domains for putative protease and reverse transcriptase of hepatitis B virus. J Virol 63: 4165-4171. doi: 10.1128/JVI.63.10.4165-4171.1989
    [112] Soussan P, Tuveri R, Nalpas B, et al. (2003) The expression of hepatitis B spliced protein (HBSP) encoded by a spliced hepatitis B virus RNA is associated with viral replication and liver fibrosis. J Hepato 38: 343-348. doi: 10.1016/S0168-8278(02)00422-1
    [113] Le Pogam S, Chua PK, Newman M, et al. (2005) Exposure of RNA templates and encapsidation of spliced viral RNA are influenced by the arginine-rich domain of human hepatitis B virus core antigen (HBcAg165–173). J Virol 79: 1871-1887. doi: 10.1128/JVI.79.3.1871-1887.2005
    [114] Bartenschlager R, Junker-Niepmann M, Schaller H (1990) The P gene product of hepatitis B virus is required as a structural component for genomic RNA encapsidation. J Virol 64: 5324-5332. doi: 10.1128/JVI.64.11.5324-5332.1990
    [115] Marschenz S, Brinckmann A, Nürnberg P, et al. (2008) Co-replication analyses of naturally occurring defective hepatitis B virus variants with wild-type. Virology 372: 247-259. doi: 10.1016/j.virol.2007.10.039
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