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Molecular biology of hepatitis B virus: effect of nucleotide substitutions on the clinical features of chronic hepatitis B

  • SPECIAL REVIEW SERIES: Molecular morphological approaches to the pathophysiology of liver disease
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Abstract

Hepatitis B virus (HBV) is a major cause of liver disease worldwide. It is covered with envelope (surface antigen) proteins with the nucleocapsid (core antigen) inside. In the nucleocapsid, there is an incomplete double-stranded DNA and a DNA polymerase. Four genes, S, C, X, and P, are encoded, and these partially overlap. Mutations have been reported in each gene and in their promoter regions, and these mutations can change the efficiency of HBV replication and the clinical course of patients. In this article, we review the relationship between the molecular biology of HBV and its clinical outcome.

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References

  1. J Summers WS Mason (1982) ArticleTitleReplication of the genome of a hepatitis B-like virus by reverse transcription of an RNA intermediate Cell 29 403–415 Occurrence Handle6180831 Occurrence Handle1:CAS:528:DyaL38Xks1Ojurg%3D Occurrence Handle10.1016/0092-8674(82)90157-X

    Article  PubMed  CAS  Google Scholar 

  2. H Okamoto F Tsuda Y Akahane Y Sugai M Yoshiba K Moriyama T Tanaka Y Miyakawa M Mayumi (1994) ArticleTitleHepatitis B virus with mutations in the core promoter for an e antigen-negative phenotype in carriers with antibody to e antigen J Virol 68 8102–8110 Occurrence Handle7966600 Occurrence Handle1:CAS:528:DyaK2MXitFyls7k%3D

    PubMed  CAS  Google Scholar 

  3. M Sterneck S Gunther J Gerlach NV Naoumov T Santantonio L Fischer X Rogiers H Greten R Williams H Will (1997) ArticleTitleHepatitis B virus sequence changes evolving in liver transplant recipients with fulminant hepatitis J Hepatol 26 754–764 Occurrence Handle9126786 Occurrence Handle1:CAS:528:DyaK2sXivVGntbc%3D Occurrence Handle10.1016/S0168-8278(97)80239-5

    Article  PubMed  CAS  Google Scholar 

  4. MA Petit S Dubanchet F Capel P Voet C Dauguet P Hauser (1991) ArticleTitleHepG2 cell binding activities of different hepatitis B virus isolates: inhibitory effect of anti-HBs and anti-preS1 (21–47) Virology 180 483–491 Occurrence Handle1703368 Occurrence Handle1:CAS:528:DyaK3MXhtF2qsr4%3D Occurrence Handle10.1016/0042-6822(91)90062-G

    Article  PubMed  CAS  Google Scholar 

  5. D Fernholz PR Galle M Stemler M Brunetto F Bonino H Will (1993) ArticleTitleInfectious hepatitis B virus variant defective in pre-S2 protein expression in a chronic carrier Virology 194 137–148 Occurrence Handle8480417 Occurrence Handle1:CAS:528:DyaK3sXmtVSrtL0%3D Occurrence Handle10.1006/viro.1993.1243

    Article  PubMed  CAS  Google Scholar 

  6. C Trautwein H Schrem HL Tillmann S Kubicka D Walker KH Boker HJ Maschek R Pichlmayr MP Manns (1996) ArticleTitleHepatitis B virus mutations in the pre-S genome before and after liver transplantation Hepatology 24 482–488 Occurrence Handle8781311 Occurrence Handle1:CAS:528:DyaK28XlvVCrsrk%3D

    PubMed  CAS  Google Scholar 

  7. T Pollicino AR Zanetti I Cacciola MA Petit A Smedile S Campo L Sagliocca M Pasquali E Tanzi G Longo G Raimondo (1997) ArticleTitlePre-S2 defective hepatitis B virus infection in patients with fulminant hepatitis Hepatology 26 495–499 Occurrence Handle9252165 Occurrence Handle1:STN:280:DyaK2szpsVCntQ%3D%3D Occurrence Handle10.1002/hep.510260235

    Article  PubMed  CAS  Google Scholar 

  8. T Santantonio MC Jung R Schneider D Fernholz M Milella L Monno G Pastore GR Pape H Will (1992) ArticleTitleHepatitis 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 Occurrence Handle1585662 Occurrence Handle1:CAS:528:DyaK38Xkt1Cjtro%3D Occurrence Handle10.1016/0042-6822(92)90559-8

    Article  PubMed  CAS  Google Scholar 

  9. H Okamoto F Tsuda H Sakugawa RI Sastrosoewignjo M Imai Y Miyakawa M Mayumi (1988) ArticleTitleTyping hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes J Gen Virol 69 IssueIDpt 10 2575–2583 Occurrence Handle3171552 Occurrence Handle1:CAS:528:DyaL1MXktVWltr4%3D

    PubMed  CAS  Google Scholar 

  10. O Yokosuka M Omata K Hosoda M Tada T Ehata M Ohto (1991) ArticleTitleDetection and direct sequencing of hepatitis B virus genome by DNA amplification method Gastroenterology 100 175–181 Occurrence Handle1983819 Occurrence Handle1:CAS:528:DyaK3MXit1aktb8%3D

    PubMed  CAS  Google Scholar 

  11. E Orito T Ichida H Sakugawa M Sata N Horiike K Hino K Okita T Okanoue S Iino E Tanaka K Suzuki H Watanabe S Hige M Mizokami (2001) ArticleTitleGeographic distribution of hepatitis B virus (HBV) genotype in patients with chronic HBV infection in Japan Hepatology 34 590–594 Occurrence Handle11526547 Occurrence Handle1:STN:280:DC%2BD3Mvot1ykug%3D%3D Occurrence Handle10.1053/jhep.2001.27221

    Article  PubMed  CAS  Google Scholar 

  12. E Hildt S Urban U Lauer PH Hofschneider AS Kekule (1993) ArticleTitleER-localization and functional expression of the HBV transactivator MHBst Oncogene 8 3359–3367 Occurrence Handle8247538 Occurrence Handle1:CAS:528:DyaK2cXkvFOgug%3D%3D

    PubMed  CAS  Google Scholar 

  13. E Hildt G Saher V Bruss PH Hofschneider (1996) ArticleTitleThe hepatitis B virus large surface protein (LHBs) is a transcriptional activator Virology 225 235–239 Occurrence Handle8918553 Occurrence Handle1:CAS:528:DyaK28XmvFGjtrk%3D Occurrence Handle10.1006/viro.1996.0594

    Article  PubMed  CAS  Google Scholar 

  14. YF Fan CC Lu WC Chen WJ Yao HC Wang TT Chang HY Lei AL Shiau IJ Su (2001) ArticleTitlePrevalence and significance of hepatitis B virus (HBV) pre-S mutants in serum and liver at different replicative stages of chronic HBV infection Hepatology 33 277–286 Occurrence Handle11124846 Occurrence Handle1:STN:280:DC%2BD3M%2FpvFSjuw%3D%3D Occurrence Handle10.1053/jhep.2001.21163

    Article  PubMed  CAS  Google Scholar 

  15. PC Tai FM Suk WH Gerlich AR Neurath C Shih (2002) ArticleTitleHypermodification and immune escape of an internally deleted middle-envelope (M) protein of frequent and predominant hepatitis B virus variants Virology 292 44–58 Occurrence Handle11878907 Occurrence Handle1:CAS:528:DC%2BD38Xktl2gsQ%3D%3D Occurrence Handle10.1006/viro.2001.1239

    Article  PubMed  CAS  Google Scholar 

  16. HC Wang HC Wu CF Chen N Fausto HY Lei IJ Su (2003) ArticleTitleDifferent types of ground glass hepatocytes in chronic hepatitis B virus infection contain specific pre-S mutants that may induce endoplasmic reticulum stress Am J Pathol 163 2441–2449 Occurrence Handle14633616 Occurrence Handle1:CAS:528:DC%2BD2cXkslKq

    PubMed  CAS  Google Scholar 

  17. HC Wang WT Chang WW Chang HC Wu W Huang HY Lei MD Lai N Fausto IJ Su (2005) ArticleTitleHepatitis B virus pre-S2 mutant upregulates cyclin A expression and induces nodular proliferation of hepatocytes Hepatology 41 761–770 Occurrence Handle15726643 Occurrence Handle1:CAS:528:DC%2BD2MXjsV2msLo%3D Occurrence Handle10.1002/hep.20615

    Article  PubMed  CAS  Google Scholar 

  18. S Locarnini J McMillan A Bartholomeusz (2003) ArticleTitleThe hepatitis B virus and common mutants Semin Liver Dis 23 5–20 Occurrence Handle12616447 Occurrence Handle1:CAS:528:DC%2BD3sXisFamtro%3D Occurrence Handle10.1055/s-2003-37587

    Article  PubMed  CAS  Google Scholar 

  19. CT Bock S Kubicka MP Manns C Trautwein (1999) ArticleTitleTwo control elements in the hepatitis B virus S-promoter are important for full promoter activity mediated by CCAAT-binding factor Hepatology 29 1236–1247 Occurrence Handle10094970 Occurrence Handle1:CAS:528:DyaK1MXisVKgsbc%3D Occurrence Handle10.1002/hep.510290426

    Article  PubMed  CAS  Google Scholar 

  20. AK Raney HB Le A McLachlan (1992) ArticleTitleRegulation of transcription from the hepatitis B virus major surface antigen promoter by the Sp1 transcription factor J Virol 66 6912–6921 Occurrence Handle1331502 Occurrence Handle1:CAS:528:DyaK3sXhslCisw%3D%3D

    PubMed  CAS  Google Scholar 

  21. Y Shaul R Ben-Levy T De-Medina (1986) ArticleTitleHigh affinity binding site for nuclear factor I next to the hepatitis B virus S gene promoter EMBO J 5 1967–1971 Occurrence Handle3463507 Occurrence Handle1:CAS:528:DyaL28Xlt1ymsLo%3D

    PubMed  CAS  Google Scholar 

  22. WF Carman AR Zanetti P Karayiannis J Waters G Manzillo E Tanzi AJ Zuckerman HC Thomas (1990) ArticleTitleVaccine-induced escape mutant of hepatitis B virus Lancet 336 325–329 Occurrence Handle1697396 Occurrence Handle1:STN:280:DyaK3czmt12ktA%3D%3D Occurrence Handle10.1016/0140-6736(90)91874-A

    Article  PubMed  CAS  Google Scholar 

  23. WF Carman C Trautwein FJ van Deursen K Colman E Dornan G McIntyre J Waters V Kliem R Muller HC Thomas MP Manns (1996) ArticleTitleHepatitis B virus envelope variation after transplantation with and without hepatitis B immune globulin prophylaxis Hepatology 24 489–493 Occurrence Handle8781312 Occurrence Handle1:STN:280:DyaK28znsV2gsg%3D%3D

    PubMed  CAS  Google Scholar 

  24. U Protzer-Knolle U Naumann R Bartenschlager T Berg U Hopf KH Meyer zum Buschenfelde P Neuhaus G Gerken (1998) ArticleTitleHepatitis 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 Occurrence Handle9425945 Occurrence Handle1:CAS:528:DyaK1cXlvVCisg%3D%3D Occurrence Handle10.1002/hep.510270138

    Article  PubMed  CAS  Google Scholar 

  25. B Bottcher SA Wynne RA Crowther (1997) ArticleTitleDetermination of the fold of the core protein of hepatitis B virus by electron cryomicroscopy Nature (Lond) 386 88–91 Occurrence Handle1:CAS:528:DyaK2sXhslCnsb4%3D Occurrence Handle10.1038/386088a0

    Article  CAS  Google Scholar 

  26. SA Wynne RA Crowther AG Leslie (1999) ArticleTitleThe crystal structure of the human hepatitis B virus capsid Mol Cell 3 771–780 Occurrence Handle10394365 Occurrence Handle1:CAS:528:DyaK1MXktlOktbs%3D Occurrence Handle10.1016/S1097-2765(01)80009-5

    Article  PubMed  CAS  Google Scholar 

  27. JF Conway N Cheng A Zlotnick PT Wingfield SJ Stahl AC Steven (1997) ArticleTitleVisualization of a 4-helix bundle in the hepatitis B virus capsid by cryo-electron microscopy Nature (Lond) 386 91–94 Occurrence Handle1:CAS:528:DyaK2sXhslCnsb8%3D Occurrence Handle10.1038/386091a0

    Article  CAS  Google Scholar 

  28. JF Conway N Cheng A Zlotnick SJ Stahl PT Wingfield DM Belnap U Kanngiesser M Noah AC Steven (1998) ArticleTitleHepatitis B virus capsid: localization of the putative immunodominant loop (residues 78 to 83) on the capsid surface, and implications for the distinction between c and e-antigens J Mol Biol 279 1111–1121 Occurrence Handle9642088 Occurrence Handle1:CAS:528:DyaK1cXktlajs74%3D Occurrence Handle10.1006/jmbi.1998.1845

    Article  PubMed  CAS  Google Scholar 

  29. PP Scaglioni M Melegari JR Wands (1997) ArticleTitlePosttranscriptional regulation of hepatitis B virus replication by the precore protein J Virol 71 345–353 Occurrence Handle8985356 Occurrence Handle1:CAS:528:DyaK28XnsF2hurg%3D

    PubMed  CAS  Google Scholar 

  30. DR Milich JE Jones JL Hughes J Price AK Raney A McLachlan (1990) ArticleTitleIs a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero? Proc Natl Acad Sci U S A 87 6599–6603 Occurrence Handle2395863 Occurrence Handle1:CAS:528:DyaK3cXmtV2rsLc%3D Occurrence Handle10.1073/pnas.87.17.6599

    Article  PubMed  CAS  Google Scholar 

  31. M Seifer DN Standring (1995) ArticleTitleAssembly and antigenicity of hepatitis B virus core particles Intervirology 38 47–62 Occurrence Handle8666524 Occurrence Handle1:CAS:528:DyaK28XltFGhtQ%3D%3D

    PubMed  CAS  Google Scholar 

  32. K Takahashi S Kishimoto K Ohori H Yoshizawa A Machida H Ohnuma F Tsuda E Munekata Y Miyakawa M Mayumi (1991) ArticleTitleMolecular heterogeneity of e antigen polypeptides in sera from carriers of hepatitis B virus J Immunol 147 3156–3160 Occurrence Handle1717588 Occurrence Handle1:CAS:528:DyaK38XkvVaq

    PubMed  CAS  Google Scholar 

  33. G Wasenauer J Kock HJ Schlicht (1992) ArticleTitleA cysteine and a hydrophobic sequence in the noncleaved portion of the pre-C leader peptide determine the biophysical properties of the secretory core protein (HBe protein) of human hepatitis B virus J Virol 66 5338–5346 Occurrence Handle1501277 Occurrence Handle1:CAS:528:DyaK38Xmt1ylsb8%3D

    PubMed  CAS  Google Scholar 

  34. P MacKay J Lees K Murray (1981) ArticleTitleThe conversion of hepatitis B core antigen synthesized in E coli into e antigen J Med Virol 8 237–243 Occurrence Handle7038044 Occurrence Handle1:CAS:528:DyaL38Xms12ksg%3D%3D

    PubMed  CAS  Google Scholar 

  35. K Takahashi M Imai T Gotanda T Sano A Oinuma S Mishiro Y Miyakawa M Mayumi (1980) ArticleTitleHepatitis B e antigen polypeptides isolated from sera of individuals infected with hepatitis B virus: comparison with HBeAg polypeptide derived from Dane particles J Gen Virol 50 49–57 Occurrence Handle7441214 Occurrence Handle1:CAS:528:DyaL3MXmtlGjuw%3D%3D

    PubMed  CAS  Google Scholar 

  36. S Hosono PC Tai W Wang M Ambrose DG Hwang TT Yuan BH Peng CS Yang CS Lee C Shih (1995) ArticleTitleCore antigen mutations of human hepatitis B virus in hepatomas accumulate in MHC class II-restricted T cell epitopes Virology 212 151–162 Occurrence Handle7545853 Occurrence Handle1:CAS:528:DyaK2MXotFajtr0%3D Occurrence Handle10.1006/viro.1995.1463

    Article  PubMed  CAS  Google Scholar 

  37. T Ehata M Omata O Yokosuka K Hosoda M Ohto (1992) ArticleTitleVariations in codons 84–101 in the core nucleotide sequence correlate with hepatocellular injury in chronic hepatitis B virus infection J Clin Invest 89 332–338 Occurrence Handle1729279 Occurrence Handle1:CAS:528:DyaK38XhtVemtLo%3D

    PubMed  CAS  Google Scholar 

  38. WL Chuang M Omata T Ehata O Yokosuka Y Ito F Imazeki SN Lu WY Chang M Ohto (1993) ArticleTitlePrecore mutations and core clustering mutations in chronic hepatitis B virus infection Gastroenterology 104 263–271 Occurrence Handle8419250 Occurrence Handle1:CAS:528:DyaK3sXitFSntb0%3D

    PubMed  CAS  Google Scholar 

  39. SL Tsai MH Chen CT Yeh CM Chu AN Lin FH Chiou TH Chang YF Liaw (1996) ArticleTitlePurification and characterization of a naturally processed hepatitis B virus peptide recognized by CD8+ cytotoxic T lymphocytes J Clin Invest 97 577–584 Occurrence Handle8567982 Occurrence Handle1:CAS:528:DyaK28Xht1Ols7o%3D

    PubMed  CAS  Google Scholar 

  40. WF Carman MR Jacyna S Hadziyannis P Karayiannis MJ McGarvey A Makris HC Thomas (1989) ArticleTitleMutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection Lancet 2 588–591 Occurrence Handle2570285 Occurrence Handle1:STN:280:DyaL1MzmtlOqsw%3D%3D Occurrence Handle10.1016/S0140-6736(89)90713-7

    Article  PubMed  CAS  Google Scholar 

  41. M Omata T Ehata O Yokosuka K Hosoda M Ohto (1991) ArticleTitleMutations in the precore region of hepatitis B virus DNA in patients with fulminant and severe hepatitis N Engl J Med 324 1699–1704 Occurrence Handle2034246 Occurrence Handle1:STN:280:DyaK3M3jvV2isg%3D%3D Occurrence Handle10.1056/NEJM199106133242404

    Article  PubMed  CAS  Google Scholar 

  42. T Imamura O Yokosuka T Kurihara T Kanda K Fukai F Imazeki H Saisho (2003) ArticleTitleDistribution of hepatitis B viral genotypes and mutations in the core promoter and precore regions in acute forms of liver disease in patients from Chiba Japan Gut 52 1630–1637 Occurrence Handle14570734 Occurrence Handle1:CAS:528:DC%2BD3sXpsFyks7w%3D Occurrence Handle10.1136/gut.52.11.1630

    Article  PubMed  CAS  Google Scholar 

  43. T Laskus DH Persing MJ Nowicki JW Mosley J Rakela (1993) ArticleTitleNucleotide sequence analysis of the precore region in patients with fulminant hepatitis B in the United States Gastroenterology 105 1173–1178 Occurrence Handle8405863 Occurrence Handle1:STN:280:DyaK2c%2FhtVWgsw%3D%3D

    PubMed  CAS  Google Scholar 

  44. H Okamoto S Yotsumoto Y Akahane T Yamanaka Y Miyazaki Y Sugai F Tsuda T Tanaka Y Miyakawa M Mayumi (1990) ArticleTitleHepatitis B viruses with precore region defects prevail in persistently infected hosts along with seroconversion to the antibody against e antigen J Virol 64 1298–1303 Occurrence Handle2304145 Occurrence Handle1:CAS:528:DyaK3cXitFWltrc%3D

    PubMed  CAS  Google Scholar 

  45. F Rodriguez-Frias M Buti R Jardi M Cotrina L Viladomiu R Esteban J Guardia (1995) ArticleTitleHepatitis B virus infection: precore mutants and its relation to viral genotypes and core mutations Hepatology 22 1641–1647 Occurrence Handle7489968 Occurrence Handle1:CAS:528:DyaK28XmvV2lsA%3D%3D Occurrence Handle10.1016/0270-9139(95)90185-X

    Article  PubMed  CAS  Google Scholar 

  46. TT Yuan A Faruqi JW Shih C Shih (1995) ArticleTitleThe mechanism of natural occurrence of two closely linked HBV precore predominant mutations Virology 211 144–156 Occurrence Handle7645207 Occurrence Handle1:CAS:528:DyaK2MXntlWjs7o%3D Occurrence Handle10.1006/viro.1995.1387

    Article  PubMed  CAS  Google Scholar 

  47. VE Buckwold Z Xu M Chen TS Yen JH Ou (1996) ArticleTitleEffects of a naturally occurring mutation in the hepatitis B virus basal core promoter on precore gene expression and viral replication J Virol 70 5845–5851 Occurrence Handle8709203 Occurrence Handle1:CAS:528:DyaK28XkvFGhs70%3D

    PubMed  CAS  Google Scholar 

  48. VE Buckwold Z Xu TS Yen JH Ou (1997) ArticleTitleEffects 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 IssueIDpt 8 2055–2065 Occurrence Handle9267007 Occurrence Handle1:CAS:528:DyaK2sXkvFCjt7s%3D

    PubMed  CAS  Google Scholar 

  49. J Li Z Xu Y Zheng DL Johnson JH Ou (2002) ArticleTitleRegulation of hepatocyte nuclear factor 1 activity by wild-type and mutant hepatitis B virus X proteins J Virol 76 5875–5881 Occurrence Handle12021320 Occurrence Handle1:CAS:528:DC%2BD38XktlSru74%3D Occurrence Handle10.1128/JVI.76.12.5875-5881.2002

    Article  PubMed  CAS  Google Scholar 

  50. K Takahashi Y Ohta K Kanai Y Akahane Y Iwasa K Hino N Ohno H Yoshizawa S Mishiro (1999) ArticleTitleClinical implications of mutations C-to-T1653 and T-to-C/A/G1753 of hepatitis B virus genotype C genome in chronic liver disease Arch Virol 144 1299–1308 Occurrence Handle10481738 Occurrence Handle1:CAS:528:DyaK1MXls12isbs%3D Occurrence Handle10.1007/s007050050588

    Article  PubMed  CAS  Google Scholar 

  51. A Honda O Yokosuka T Ehata M Tagawa F Imazeki H Saisho (1999) ArticleTitleDetection of mutations in the enhancer 2/core promoter region of hepatitis B virus in patients with chronic hepatitis B virus infection: comparison with mutations in precore and core regions in relation to clinical status J Med Virol 57 337–344 Occurrence Handle10089043 Occurrence Handle1:CAS:528:DyaK1MXhvFyjtLc%3D Occurrence Handle10.1002/(SICI)1096-9071(199904)57:4<337::AID-JMV2>3.0.CO;2-L

    Article  PubMed  CAS  Google Scholar 

  52. T Shaw SA Locarnini (1995) ArticleTitleHepatic purine and pyrimidine metabolism: implications for antiviral chemotherapy of viral hepatitis Liver 15 169–184 Occurrence Handle8544639 Occurrence Handle1:STN:280:DyaK28%2FmsVamsA%3D%3D

    PubMed  CAS  Google Scholar 

  53. J Li VE Buckwold MW Hon JH Ou (1999) ArticleTitleMechanism of suppression of hepatitis B virus precore RNA transcription by a frequent double mutation J Virol 73 1239–1244 Occurrence Handle9882327 Occurrence Handle1:CAS:528:DyaK1MXmtlajug%3D%3D

    PubMed  CAS  Google Scholar 

  54. H Lee HT Kim Y Yun (1998) ArticleTitleLiver-specific enhancer II is the target for the p53-mediated inhibition of hepatitis B viral gene expression J Biol Chem 273 19786–19791 Occurrence Handle9677410 Occurrence Handle1:CAS:528:DyaK1cXlt1Citbk%3D Occurrence Handle10.1074/jbc.273.31.19786

    Article  PubMed  CAS  Google Scholar 

  55. J Li Ou JH (2001) ArticleTitleDifferential regulation of hepatitis B virus gene expression by the Sp1 transcription factor J Virol 75 8400–8406 Occurrence Handle11507185 Occurrence Handle1:CAS:528:DC%2BD3MXmsVaruro%3D Occurrence Handle10.1128/JVI.75.18.8400-8406.2001

    Article  PubMed  CAS  Google Scholar 

  56. H Tu C Bonura C Giannini H Mouly P Soussan M Kew P Paterlini-Brechot C Brechot D Kremsdorf (2001) ArticleTitleBiological impact of natural COOH-terminal deletions of hepatitis B virus X protein in hepatocellular carcinoma tissues Cancer Res 61 7803–7810 Occurrence Handle11691796 Occurrence Handle1:CAS:528:DC%2BD3MXotlakurk%3D

    PubMed  CAS  Google Scholar 

  57. Y Wang SH Lau JS Sham MC Wu T Wang XY Guan (2004) ArticleTitleCharacterization of HBV integrants in 14 hepatocellular carcinomas: association of truncated X gene and hepatocellular carcinogenesis Oncogene 23 142–148 Occurrence Handle14712219 Occurrence Handle1:CAS:528:DC%2BD2cXhtlGjuw%3D%3D Occurrence Handle10.1038/sj.onc.1206889

    Article  PubMed  CAS  Google Scholar 

  58. G Radziwill W Tucker H Schaller (1990) ArticleTitleMutational analysis of the hepatitis B virus P gene product: domain structure and RNase H activity J Virol 64 613–620 Occurrence Handle2153228 Occurrence Handle1:CAS:528:DyaK3cXpsVGktg%3D%3D

    PubMed  CAS  Google Scholar 

  59. R Bartenschlager M Junker-Niepmann H Schaller (1990) ArticleTitleThe P gene product of hepatitis B virus is required as a structural component for genomic RNA encapsidation J Virol 64 5324–5332 Occurrence Handle2214019 Occurrence Handle1:CAS:528:DyaK3cXmt1Ors78%3D

    PubMed  CAS  Google Scholar 

  60. R Bartenschlager H Schaller (1992) ArticleTitleHepadnaviral assembly is initiated by polymerase binding to the encapsidation signal in the viral RNA genome EMBO J 11 3413–3420 Occurrence Handle1380455 Occurrence Handle1:CAS:528:DyaK38Xls1Ont7c%3D

    PubMed  CAS  Google Scholar 

  61. JR Pollack D Ganem (1994) ArticleTitleSite-specific RNA binding by a hepatitis B virus reverse transcriptase initiates two distinct reactions: RNA packaging and DNA synthesis J Virol 68 5579–5587 Occurrence Handle7520092 Occurrence Handle1:CAS:528:DyaK2cXlvFOms78%3D

    PubMed  CAS  Google Scholar 

  62. K Das X Xiong H Yang CE Westland CS Gibbs SG Sarafianos E Arnold (2001) ArticleTitleMolecular modeling and biochemical characterization reveal the mechanism of hepatitis B virus polymerase resistance to lamivudine (3TC) and emtricitabine (FTC) J Virol 75 4771–4779 Occurrence Handle11312349 Occurrence Handle1:STN:280:DC%2BD3M3it1egsA%3D%3D Occurrence Handle10.1128/JVI.75.10.4771-4779.2001

    Article  PubMed  CAS  Google Scholar 

  63. T Seta O Yokosuka F Imazeki M Tagawa H Saisho (2000) ArticleTitleEmergence of YMDD motif mutants of hepatitis B virus during lamivudine treatment of immunocompetent type B hepatitis patients J Med Virol 60 8–16 Occurrence Handle10568756 Occurrence Handle1:CAS:528:DC%2BD3cXit1ygtQ%3D%3D Occurrence Handle10.1002/(SICI)1096-9071(200001)60:1<8::AID-JMV2>3.0.CO;2-U

    Article  PubMed  CAS  Google Scholar 

  64. LJ Stuyver SA Locarnini A Lok DD Richman WF Carman JL Dienstag RF Schinazi (2001) ArticleTitleNomenclature for antiviral-resistant human hepatitis B virus mutations in the polymerase region Hepatology 33 751–757 Occurrence Handle11230757 Occurrence Handle1:CAS:528:DC%2BD3MXit1emtb8%3D Occurrence Handle10.1053/jhep.2001.22166

    Article  PubMed  CAS  Google Scholar 

  65. MI Allen M Deslauriers CW Andrews GA Tipples KA Walters DL Tyrrell N Brown LD Condreay (1998) ArticleTitleIdentification and characterization of mutations in hepatitis B virus resistant to lamivudine. Lamivudine Clinical Investigation Group Hepatology 27 1670–1677 Occurrence Handle9620341 Occurrence Handle1:CAS:528:DyaK1cXjvVCrsrY%3D Occurrence Handle10.1002/hep.510270628

    Article  PubMed  CAS  Google Scholar 

  66. GA Tipples MM Ma KP Fischer VG Bain NM Kneteman DL Tyrrell (1996) ArticleTitleMutation in HBV RNA-dependent DNA polymerase confers resistance to lamivudine in vivo Hepatology 24 714–717 Occurrence Handle8781348 Occurrence Handle1:CAS:528:DyaK28XlvVCrtLs%3D

    PubMed  CAS  Google Scholar 

  67. MF Yuen E Sablon CK Hui HJ Yuan H Decraemer CL Lai (2001) ArticleTitleFactors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy Hepatology 34 785–791 Occurrence Handle11584376 Occurrence Handle1:CAS:528:DC%2BD3MXns1Kisrc%3D Occurrence Handle10.1053/jhep.2001.27563

    Article  PubMed  CAS  Google Scholar 

  68. SK Ono-Nita N Kato Y Shiratori T Masaki KH Lan FJ Carrilho M Omata (1999) ArticleTitleYMDD motif in hepatitis B virus DNA polymerase influences on replication and lamivudine resistance: a study by in vitro full-length viral DNA transfection Hepatology 29 939–945 Occurrence Handle10051501 Occurrence Handle1:CAS:528:DyaK1MXhvFyjsLY%3D Occurrence Handle10.1002/hep.510290340

    Article  PubMed  CAS  Google Scholar 

  69. SK Ono N Kato Y Shiratori J Kato T Goto RF Schinazi FJ Carrilho M Omata (2001) ArticleTitleThe polymerase L528M mutation cooperates with nucleotide binding-site mutations, increasing hepatitis B virus replication and drug resistance J Clin Invest 107 449–455 Occurrence Handle11181644 Occurrence Handle1:CAS:528:DC%2BD3MXhtlWktLY%3D Occurrence Handle10.1172/JCI11100

    Article  PubMed  CAS  Google Scholar 

  70. J Ding K Das Y Hsiou SG Sarafianos AD Clark SuffixJr A Jacobo-Molina C Tantillo SH Hughes E Arnold (1998) ArticleTitleStructure and functional implications of the polymerase active site region in a complex of HIV-1 RT with a double-stranded DNA template-primer and an antibody Fab fragment at 2.8 A resolution J Mol Biol 284 1095–1111 Occurrence Handle9837729 Occurrence Handle1:CAS:528:DyaK1MXivFCiuw%3D%3D Occurrence Handle10.1006/jmbi.1998.2208

    Article  PubMed  CAS  Google Scholar 

  71. H Huang R Chopra GL Verdine SC Harrison (1998) ArticleTitleStructure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance Science 282 1669–1675 Occurrence Handle9831551 Occurrence Handle1:CAS:528:DyaK1cXnslGhtr4%3D Occurrence Handle10.1126/science.282.5394.1669

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Medicine and Clinical Oncology (K1), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, 260-8670, Japan

    Osamu Yokosuka & Makoto Arai

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  1. Osamu Yokosuka
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  2. Makoto Arai
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Correspondence to Osamu Yokosuka.

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Yokosuka, O., Arai, M. Molecular biology of hepatitis B virus: effect of nucleotide substitutions on the clinical features of chronic hepatitis B. Med Mol Morphol 39, 113–120 (2006). https://doi.org/10.1007/s00795-006-0328-5

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  • DOI: https://doi.org/10.1007/s00795-006-0328-5

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