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Hepatitis B Virus Infection pp 39–69Cite as

The Regulation of HBV Transcription and Replication

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1179))

Abstract

Hepatitis B virus (HBV) is a major human pathogen lacking a reliable curative therapy. Current therapeutics target the viral reverse transcriptase/DNA polymerase to inhibit viral replication but generally fail to resolve chronic HBV infections. Due to the limited coding potential of the HBV genome, alternative approaches for the treatment of chronic infections are desperately needed. An alternative approach to the development of antiviral therapeutics is to target cellular gene products that are critical to the viral life cycle. As transcription of the viral genome is an essential step in the viral life cycle, the selective inhibition of viral RNA synthesis is a possible approach for the development of additional therapeutic modalities that might be used in combination with currently available therapies. To address this possibility, a molecular understanding of the relationship between viral transcription and replication is required. The first step is to identify the transcription factors that are the most critical in controlling the levels of HBV RNA synthesis and to determine their in vivo role in viral biosynthesis. Mapping studies in cell culture utilizing reporter gene constructs permitted the identification of both ubiquitous and liver-enriched transcription factors capable of modulating transcription from the four HBV promoters. However, it was challenging to determine their relative importance for viral biosynthesis in the available human hepatoma replication systems. This technical limitation was addressed, in part, by the development of non-hepatoma HBV replication systems where viral biosynthesis was dependent on complementation with exogenously expressed transcription factors. These systems revealed the importance of specific nuclear receptors and hepatocyte nuclear factor 3 (HNF3)/forkhead box A (FoxA) transcription factors for HBV biosynthesis. Furthermore, using the HBV transgenic mouse model of chronic viral infection, the importance of various nuclear receptors and FoxA isoforms could be established in vivo. The availability of this combination of systems now permits a rational approach toward the development of selective host transcription factor inhibitors. This might permit the development of a new class of therapeutics to aid in the treatment and resolution of chronic HBV infections, which currently affects approximately 1 in 30 individuals worldwide and kills up to a million people annually.

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References

  1. Seeger C, Mason WS (2015) Molecular biology of hepatitis B virus infection. Virology 479–480:672–686

    Article  PubMed  CAS  Google Scholar 

  2. Vaudin M, Wolstenholme AJ, Tsiquay KN, Zuckerman AJ, Harrison TJ (1988) The complete nucleotide sequence of the genome of a hepatitis B virus isolated from a naturally infected chimpanzee. J Gen Virol 69:1383–1389

    Article  CAS  PubMed  Google Scholar 

  3. Lichter EA (1969) Chimpanzee antibodies to Australia antigen. Nature 224:810–811

    Article  CAS  PubMed  Google Scholar 

  4. Maynard JE, Hartwell WV, Berquist KR (1971) Hepatitis-associated antigen in chimpanzees. J Infect Dis 123:660–664

    Article  CAS  PubMed  Google Scholar 

  5. Hirschman RJ, Shulman R, Barker LF, Smith KO (1969) Virus-like particles in sera of patients with infectious and serum hepatitis. JAMA 208:1667–1670

    Article  CAS  PubMed  Google Scholar 

  6. Barker LF, Maynard JE, Purcell RH, Hoofnagle JH, Berquist KR, London WT (1975) Viral hepatitis, type B, in experimental animals. Am J Med Sci 270:189–194

    Article  CAS  PubMed  Google Scholar 

  7. Maynard JE, Berquist KR, Krushak DH, Purcell RH (1972) Experimental infection of chimpanzees with the virus of hepatitis B. Nature 237:514–515

    Article  CAS  PubMed  Google Scholar 

  8. Acs G, Sells MA, Purcell RH, Price P, Engle R, Shapiro M et al (1987) Hepatitis B virus produced by transfected HepG2 cells causes hepatitis in chimpanzees. Proc Natl Acad Sci USA 84:4641–4644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sureau C, Eichberg JW, Hubbard GB, Romet-Lemonne JL, Essex M (1988) A molecularly cloned hepatitis B virus produced in vitro is infectious in a chimpanzee. J Virol 62:3064–3067

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Thornton SM, Walker S, Zuckerman JN (2001) Management of hepatitis B virus infections in two gibbons and a western lowland gorilla in a zoological collection. Vet Rec 149(4):113–115

    Article  CAS  PubMed  Google Scholar 

  11. Warren KS, Heeney JL, Swan RA, Heriyanto, Verschoor EJ (1999) A new group of hepadnaviruses naturally infecting orangutans (Pongo pygmaeus). J Virol 73(9):7860–7865

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Cattaneo R, Will H, Hernandez N, Schaller H (1983) Signals regulating hepatitis B surface antigen transcription. Nature 305:336–338

    Article  CAS  PubMed  Google Scholar 

  13. Cattaneo R, Will H, Schaller H (1984) Hepatitis B virus transcription in the infected liver. EMBO J 3:2191–2196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yokosuka O, Omata M, Imazeki F, Ito Y, Okuda K (1986) Hepatitis B virus RNA transcripts and DNA in chronic liver disease. N Engl J Med 315:1187–1192

    Article  CAS  PubMed  Google Scholar 

  15. Imazeki F, Yaginuma K, Omata M, Okuda K, Kobayashi M, Koike K (1987) RNA transcripts of hepatitis B virus in hepatocellular carcinoma. Hepatology 7:753–757

    Article  CAS  PubMed  Google Scholar 

  16. T-S S, Lui W-Y, Lin L-H, Han S-H, P’eng F-K (1989) Analysis of hepatitis B virus transcripts in infected human livers. Hepatology 9:180–185

    Article  Google Scholar 

  17. Guidotti LG, Matzke B, Schaller H, Chisari FV (1995) High-level hepatitis B virus replication in transgenic mice. J Virol 69:6158–6169

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Ganem D (1982) Persistent infection of humans with hepatitis B virus: mechanisms and consequences. Rev Infect Dis 4:1026–1047

    Article  CAS  PubMed  Google Scholar 

  19. Chisari FV, Ferrari C (1995) Hepatitis B virus Immunopathogenesis. Annu Rev Immunol 13(1):29–60

    Article  CAS  PubMed  Google Scholar 

  20. Beasley RP (1988) Hepatitis B virus: the major etiology of hepatocellular carcinoma. Cancer 61:1942–1956

    Article  CAS  PubMed  Google Scholar 

  21. Beasley RP, Hwang L-Y, Lin C-C, Chien C-S (1981) Hepatocellular carcinoma and hepatitis B virus – a prospective study of 22707 men in Taiwan. Lancet 2:1129–1133

    Article  CAS  PubMed  Google Scholar 

  22. Goldstein ST, Zhou F, Hadler SC, Bell BP, Mast EE, Margolis HS (2005) A mathematical model to estimate global hepatitis B disease burden and vaccination impact. Int J Epidemiol 34(6):1329–1339

    Article  PubMed  Google Scholar 

  23. Ott JJ, Stevens GA, Groeger J, Wiersma ST (2012) Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 30(12):2212–2219

    Article  CAS  PubMed  Google Scholar 

  24. Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ (2015) Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet 386(10003):1546–1555

    Article  PubMed  Google Scholar 

  25. Terrault NA, Bzowej NH, Chang K-M, Hwang JP, Jonas MM, Murad MH (2016) AASLD guidelines for treatment of chronic hepatitis B. Hepatology 63(1):261–283

    Article  PubMed  Google Scholar 

  26. Wong DK-H, Seto W-K, Fung J, Ip P, Huang F-Y, Lai C-L et al (2013) Reduction of hepatitis B surface antigen and covalently closed circular DNA by nucleos(t)ide analogues of different potency. Clin Gastroenterol Hepatol 11(8):1004–10.e1

    Article  PubMed  CAS  Google Scholar 

  27. Galibert F, Mandart E, Fitoussi F, Tiollais P, Charnay P (1979) Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature 281:646–650

    Article  CAS  PubMed  Google Scholar 

  28. Valenzuela P, Quiroga M, Zaldivar J, Gray P, Rutter WJ (1980) The nucleotide sequence of the hepatitis B viral genome and the identification of the major viral genes. In: Fields B, Jaenisch R, Fox CF (eds) Animal virus genetics. Academic, New York, pp 57–70

    Chapter  Google Scholar 

  29. Ono Y, Onda H, Sasada R, Igarashi K, Sugino Y, Nishioka K (1983) The complete nucleotide sequences of the cloned hepatitis B virus DNA: subtype adr and adw. Nucleic Acids Res 11:1747–1757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Okamoto H, Imai M, Shimozaki M, Hoshi Y, Iizuka H, Gotanda T et al (1986) Nucleotide sequence of a cloned hepatitis B virus genome, subtype ayr: Comparison with genomes of the other three subtypes. J Gen Virol 67:2305–2314

    Article  CAS  PubMed  Google Scholar 

  31. Kramvis A, Kew M, François G (2005) Hepatitis B virus genotypes. Vaccine 23(19):2409–2423

    Article  CAS  PubMed  Google Scholar 

  32. Lamontagne RJ, Bagga S, Bouchard MJ (2016) Hepatitis B virus molecular biology and pathogenesis. Hepatoma Res 2:163–186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. McLachlan A, Milich DR, Raney AK, Riggs MG, Hughes JL, Sorge J et al (1987) Expression of hepatitis B virus surface and core antigens: influences of pre-s and precore sequences. J Virol 61:683–692

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Ou JH, Laub O, Rutter WJ (1986) Hepatitis B virus gene function: the precore region targets the core antigen to cellular membranes and causes the secretion of the e antigen. Proc Natl Acad Sci USA 83:1578–1582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Roossinck MJ, Jameel S, Loukin SH, Siddiqui A (1986) Expression of hepatitis B viral core region in mammalian cells. Mol Cell Biol 6:1393–1400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bruss V, Gerlich WH (1988) Formation of transmembranous hepatitis B e-antigen by cotranslational in vitro processing of the viral precore protein. Virology 163:268–275

    Article  CAS  PubMed  Google Scholar 

  37. Garcia PD, Ou J-H, Rutter WJ, Walter P (1988) Targeting of the hepatitis B virus precore protein to the endoplasmic reticulum membrane: after signal peptide cleavage translocation can be aborted and the product released into the cytoplasm. J Cell Biol 106:1093–1104

    Article  CAS  PubMed  Google Scholar 

  38. Standring DN, Ou J-H, Masiarz FR, Rutter WJ (1988) A signal peptide encoded within the precore region of hepatitis B virus directs the secretion of heterogeneous population of e antigens in Xenopus oocytes. Proc Natl Acad Sci USA 85:8405–8409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Takahashi K, Kishimoto S, Ohori K, Yoshizawa H, Machida A, Ohnuma H et al (1991) Molecular heterogeneity of e antigen polypeptides in sera from carriers of hepatitis B virus. J Immunol 147:3156–3160

    CAS  PubMed  Google Scholar 

  40. Takahashi K, Machida A, Funatsu G, Nomura M, Usuda S, Aoyagi S et al (1983) Immunochemical structure of hepatitis B e antigen in the serum. J Immunol 130:2903–2907

    CAS  PubMed  Google Scholar 

  41. Messageot F, Salhi S, Eon P, Rossignol JM (2003) Proteolytic processing of the hepatitis B virus e antigen precursor – cleavage at two furin consensus sequences. J Biol Chem 278(2):891–895

    Article  CAS  PubMed  Google Scholar 

  42. Ito K, Kim KH, Lok AS-F, Tong S (2009) Characterization of genotype-specific carboxyl-terminal cleavage sites of hepatitis B virus e antigen precursor and identification of furin as the candidate enzyme. J Virol 83(8):3507–3517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. DiMattia Michael A, Watts Norman R, Stahl Stephen J, Grimes Jonathan M, Steven Alasdair C, Stuart David I et al (2013) Antigenic switching of hepatitis B virus by alternative dimerization of the capsid protein. Structure 21(1):133–142

    Article  CAS  PubMed  Google Scholar 

  44. Watts NR, Vethanayagam JG, Ferns RB, Tedder RS, Harris A, Stahl SJ et al (2010) Molecular basis for the high degree of antigenic cross-reactivity between hepatitis B virus capsids (HBcAg) and dimeric capsid-related protein (HBeAg): insights into the enigmatic nature of the e-antigen. J Mol Biol 398(4):530–541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Conway JF, Cheng N, Zlotnick A, Wingfield PT, Stahl SJ, Steven AC (1997) Visualization of a 4-helix bundle in the hepatitis B virus capsid by cryo-electron microscopy. Nature 386:91–94

    Article  CAS  PubMed  Google Scholar 

  46. Wynne SA, Crowther RA, Leslie AGW (1999) The crystal structure of the human hepatitis B virus capsid. Mol Cell 3(6):771–780

    Article  CAS  PubMed  Google Scholar 

  47. Roossinck MJ, Siddiqui A (1987) In vivo phosphorylation and protein analysis of hepatitis B virus core antigen. J Virol 61:955–961

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Weimer T, Salfeld J, Will H (1987) Expression of the hepatitis B virus core gene in vitro and in vivo. J Virol 61:3109–3113

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Persing DH, Varmus HE, Ganem D (1986) Inhibition of secretion of hepatitis B surface antigen by a related presurface polypeptide. Science 234:1388–1391

    Article  CAS  PubMed  Google Scholar 

  50. Cheng K-C, Moss B (1987) Selective synthesis and secretion of particles composed of the hepatitis B virus middle surface protein directed by a recombinant vaccinia virus: induction of antibodies to pre-S and S epitopes. J Virol 61:1286–1290

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Crowley CW, Liu CC, Levinson AD (1983) Plasmid-directed synthesis of hepatitis B surface antigen in monkey cells. Mol Cell Biol 3(1):44–55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Hsiung N, Fitts R, Wilson S, Milne A, Hamer DH (1984) Efficient production of hepatitis B surface antigen using a bovine papilloma virus-metallothionein vector. J Mol App Gen 2:497–506

    CAS  Google Scholar 

  53. Moriarty AM, Hoyer BH, Shih JW-K, Gerin JL, Hamer DH (1981) Expression of the hepatitis B virus surface antigen gene in cell culture by using a simian virus 40 vector. Proc Natl Acad Sci USA 78:2606–2610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Schmitt S, Glebe D, Alving K, Tolle TK, Linder M, Geyer H et al (1999) Analysis of the pre-S2 N- and O-linked glycans of the M surface protein from human hepatitis B virus. J Biol Chem 274(17):11945–11957

    Article  CAS  PubMed  Google Scholar 

  55. Schmitt S, Glebe D, Tolle TK, Lochnit G, Linder D, Geyer R et al (2004) Structure of pre-S2 N- and O-linked glycans in surface proteins from different genotypes of hepatitis B virus. J Gen Virol 85(7):2045–2053

    Article  CAS  PubMed  Google Scholar 

  56. Mehta A, Lu XY, Block TM, Blumberg BS, Dwek RA (1997) Hepatitis B virus (HBV) envelope glycoproteins vary drastically in their sensitivity to glycan processing: evidence that alteration of a single N-linked glycosylation site can regulate HBV secretion. Proc Natl Acad Sci USA 94:1822–1827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Machida A, Kishimoto S, Ohnuma H, Miyamoto H, baba K, Oad K et al (1982) A glycopeptide containing 15 amino acid residues derived from hepatitis B surface antigen particles: demonstration of immunogenicity to raise anti-HBs in mice. Mol Immunol 19:1087–1093

    Article  CAS  PubMed  Google Scholar 

  58. Heermann KH, Goldmann U, Schwartz W, Seyffarth T, Baumgarten H, Gerlich WH (1984) Large surface proteins of hepatitis B virus containing the pre-s sequence. J Virol 52:396–402

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Bartenschlager R, Schaller H (1988) The amino-terminal domain of the hepadnaviral P-gene encodes the terminal protein (genome-linked protein) believed to prime reverse transcription. EMBO J 7:4185–4192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zoulim F, Seeger C (1994) Reverse transcription in hepatitis B viruses is primed by a tyrosine residue of the polymerase. J Virol 68:6–13

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Wang G-H, Seeger C (1992) The reverse transcriptase of hepatitis B virus acts as a protein primer for viral DNA synthesis. Cell 71:663–670

    Article  CAS  PubMed  Google Scholar 

  62. Clark DN, Flanagan JM, Hu J (2017) Mapping of functional subdomains in the terminal protein domain of hepatitis B virus polymerase. J Virol 91(3):e01785-16

    Article  PubMed  PubMed Central  Google Scholar 

  63. Weber M, Bronsema V, Bartos H, Bosserhoff A, Bartenschlager R, Schaller H (1994) Hepadnavirus P protein utilizes a tyrosine residue in the TP domain to prime reverse transcription. J Virol 68:2994–2999

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Bavand M, Feitelson M, Laub O (1989) The hepatitis B virus-associated reverse transcriptase is encoded by the viral pol gene. J Virol 63:1019–1021

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Chang L-J, Pryciak P, Ganem D, Varmus HE (1989) Biosynthesis of the reverse transcriptase of hepatitis B viruses involves de novo translational initiation not ribosomal frameshifting. Nature 337:364–368

    Article  CAS  PubMed  Google Scholar 

  66. Wang G-H, Zoulim F, Leber EH, Kitson J, Seeger C (1994) Role of RNA in enzymatic activity of the reverse transcriptase of hepatitis B viruses. J Virol 68:8437–8442

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Lanford RE, Notvall L, Lee H, Beames B (1997) Transcomplementation of nucleotide priming and reverse transcription between independently expressed TP and RT domains of the hepatitis B virus reverse transcriptase. J Virol 71:2996–3004

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Chen Y, Marion PL (1996) Amino acids essential for RNase H activity of hepadnaviruses are also required for efficient elongation of minus-strand viral DNA. J Virol 70:6151–6156

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Radziwill G, Tucker W, Schaller H (1990) Mutational analysis of the hepatitis B virus P gene product: domain structure and RNase activity. J Virol 64:613–620

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Wei X, Peterson DL (1996) Expression, purification, and characterization of an active RNase H domain of the hepatitis B viral polymerase. J Biol Chem 271:32617–32622

    Article  CAS  PubMed  Google Scholar 

  71. Ko C, Shin Y-C, Park W-J, Kim S, Kim J, Ryu W-S (2014) Residues Arg703, Asp777, and Arg781 of the RNase H domain of hepatitis B virus polymerase are critical for viral DNA synthesis. J Virol 88(1):154–163

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Zoulim F, Saputelli J, Seeger C (1994) Woodchuck hepatitis virus X protein is required for viral infection in vivo. J Virol 68:2026–2030

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Chen H-S, Kaneko S, Girones R, Anderson RW, Hornbuckle WE, Tennant BC et al (1993) The woodchuck hepatitis virus X gene is important for establishment of virus infection in woodchucks. J Virol 67:1218–1226

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Slagle BL, Bouchard MJ (2016) Hepatitis B virus X and regulation of viral gene expression. Cold Spring Harb Perspect Med 6(3):a021402

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Slagle BL, Andrisani OM, Bouchard MJ, Lee CGL, Ou JHJ, Siddiqui A (2015) Technical standards for hepatitis B virus X protein (HBx) research. Hepatology 61(4):1416–1424

    Article  CAS  PubMed  Google Scholar 

  76. Yaginuma K, Shirakata Y, Kobayashi M, Koike K (1987) Hepatitis B virus (HBV) particles are produced in a cell culture system by transient expression of transfected HBV DNA. Proc Natl Acad Sci USA 84:2678–2682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Sells MA, Zelent AZ, Shvartsman M, Acs G (1988) Replicative intermediates of hepatitis B virus in HepG2 cells that produce infectious virions. J Virol 62:2836–2844

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Farza H, Hadchouel M, Scotto J, Tiollais P, Babinet C, Pourcel C (1988) Replication and gene expression of hepatitis B virus in a transgenic mouse that contains the complete viral genome. J Virol 62:4144–4152

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Raney AK, Eggers CM, Kline EF, Guidotti LG, Pontoglio M, Yaniv M et al (2001) Nuclear covalently closed circular viral genomic DNA in the liver of hepatocyte nuclear factor 1α-null hepatitis B virus transgenic mice. J Virol 75(6):2900–2911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Sureau C, Romet-Lemonne J-L, Mullins JI, Essex M (1986) Production of hepatitis B virus by a differentiated human hepatoma cell line after transfection with cloned circular HBV DNA. Cell 47:37–47

    Article  CAS  PubMed  Google Scholar 

  81. Tsurimoto T, Fujiyama A, Matsubara K (1987) Stable expression and replication of hepatitis B virus genome in an integrated state in a human hepatoma cell line transfected with the cloned viral DNA. Proc Natl Acad Sci USA 84:444–448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Chang C, K-S J, C-P H, Lo SJ, T-S S, Ting L-P et al (1987) Production of hepatitis B virus in vitro by transient expression of cloned HBV DNA in a hepatoma cell line. EMBO J 6:675–680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kaneko S, Miller RH (1988) X-region-specific transcript in mammalian hepatitis B virus-infected liver. J Virol 62:3979–3984

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Araki K, Miyazaki J-I, Hino O, Tomita N, Chisaka O, Matsubara K et al (1989) Expression and replication of hepatitis B virus genome in transgenic mice. Proc Natl Acad Sci USA 86:207–211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Simonsen CC, Levinson AD (1983) Analysis of processing and polyadenylation signals of the hepatitis B virus surface antigen gene by using simian virus 40-hepatitis B virus chimeric plasmids. Mol Cell Biol 3:2250–2258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Gough NM (1983) Core and e antigen synthesis in rodent cells transformed with hepatitis B virus DNA is associated with greater than genome length viral messenger RNAs. J Mol Biol 165:683–699

    Article  CAS  PubMed  Google Scholar 

  87. Siddiqui A, Jameel S, Mapoles J (1986) Transcriptional control elements of hepatitis B surface antigen gene. Proc Natl Acad Sci USA 83:566–570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Saito I, Oya Y, Shimojo H (1986) Novel RNA family structure of hepatitis B virus expressed in human cells, using a helper-free adenovirus vector. J Virol 58:554–560

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Siddiqui A, Jameel S, Mapoles J (1987) Expression of the hepatitis B virus X gene in mammalian cells. Proc Natl Acad Sci USA 84:2513–2517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Honigwachs J, Faktor O, Dikstein R, Shaul Y, Laub O (1989) Liver-specific expression of hepatitis B virus is determined by the combined action of the core gene promoter and the enhancer. J Virol 63:919–924

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Roychoudhury S, Shih C (1990) Cis rescue of a mutated reverse transcriptase gene of human hepatitis B virus by creation of an internal ATG. J Virol 64:1063–1069

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Schlicht H-J, Radziwill G, Schaller H (1989) Synthesis and encapsidation of duck hepatitis B virus reverse transcriptase do not require formation of core-polymerase fusion proteins. Cell 56:85–92

    Article  CAS  PubMed  Google Scholar 

  93. Summers J, Mason WS (1982) Replication of the genome of a hepatitis B-like virus by reverse transcription of an RNA intermediate. Cell 29:403–415

    Article  CAS  PubMed  Google Scholar 

  94. Will H, Reiser W, Weimer T, Pfaff E, Buscher M, Sprengle R et al (1987) Replication strategy of human hepatitis B virus. J Virol 61:904–911

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Hirsch RC, Lavine JE, Chang L-J, Varmus HE, Ganem D (1990) Polymerase gene products of hepatitis B viruses are required for genomic RNA packaging as well as for reverse transcription. Nature 344:552–555

    Article  CAS  PubMed  Google Scholar 

  96. Stein O, Fainaru M, Stein Y (1972) Visualization of virus-like particles in endoplasmic reticulum of hepatocytes of Australia antigen carriers. Lab Invest 26:262–269

    CAS  PubMed  Google Scholar 

  97. Huang S-N, Groh V (1973) Immunoagglutination electron microscopic study on virus-like particles and Australia antigen in liver tissue. Lab Invest 29:353–366

    CAS  PubMed  Google Scholar 

  98. Yamada G, Nakane PK (1977) Hepatitis B core and surface antigens in liver tissue. Lab Invest 36:649–659

    CAS  PubMed  Google Scholar 

  99. Yamada G, Sakamoto Y, Mizuno M, Nishihara T, Kobayashi T, Takahashi T et al (1982) Electron and immunoelectron microscopic study of Dane particle formation in chronic hepatitis B virus infection. Gastroenterology 83:348–356

    CAS  PubMed  Google Scholar 

  100. Gerber MA, Sells MA, Chen M-L, Thung SN, Tabibzadeh SS, Hood A et al (1988) Morphologic, immunohistochemical, and ultrastructural studies of the production of hepatitis B virus in vitro. Lab Invest 59:173–180

    CAS  PubMed  Google Scholar 

  101. Kamimura T, Yoshikawa A, Ichida F, Sasaki H (1981) Electron microscopic studies of Dane particles in hepatocytes with special reference to intracellular development of Dane particles and their relation with HBeAg in serum. Hepatology 1:392–397

    Article  CAS  PubMed  Google Scholar 

  102. Tuttleman JS, Pourcel C, Summers J (1986) Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells. Cell 47:451–460

    Article  CAS  PubMed  Google Scholar 

  103. Standring DN, Rutter WJ, Varmus HE, Ganem D (1984) Transcription of the hepatitis B surface antigen gene in cultured murine cells initiates within the presurface region. J Virol 50:563–571

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Hu K-Q, Siddiqui A (1991) Regulation of the hepatitis B virus gene expression by the enhancer element I. Virology 181:721–726

    Article  CAS  PubMed  Google Scholar 

  105. Treinin M, Laub O (1987) Identification of a promoter element located upstream from the hepatitis B virus X gene. Mol Cell Biol 7:545–548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Tokusumi Y, Ma Y, Song X, Jacobson RH, Takada S (2007) The new core promoter element XCPE1 (X core promoter element 1) directs activator-, mediator-, and TATA-binding protein-dependent but TFIID-independent RNA polymerase II transcription from TATA-less promoters. Mol Cell Biol 27(5):1844–1858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Moriarty AM, Alexander H, Lerner RA, Thornton GB (1985) Antibodies to peptides detect new hepatitis B antigen: serological correlation with hepatocellular carcinoma. Science 227:429–433

    Article  CAS  PubMed  Google Scholar 

  108. Buckwold VE, Chen M, Ou JH (1997) Interaction of transcription factors RFX1 and MIBP1 with the gamma motif of the negative regulatory element of the hepatitis B virus core promoter. Virology 227:515–518

    Article  CAS  PubMed  Google Scholar 

  109. Zhang P, Raney AK, McLachlan A (1993) Characterization of functional Sp1 transcription factor binding sites in the hepatitis B virus nucleocapsid promoter. J Virol 67:1472–1481

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Yuh C-H, Ting L-P (1991) C/EBP-like proteins binding to the functional box-α and box-β of the second enhancer of hepatitis B virus. Mol Cell Biol 11:5044–5052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Choi BH, Park GT, Rho HM (1999) Interaction of hepatitis B viral X protein and CCAAT/enhancer-binding protein α synergistically activates the hepatitis B viral enhancer II pregenomic promoter. J Biol Chem 274(5):2858–2865

    Article  CAS  PubMed  Google Scholar 

  112. Li M, Xie YH, Kong YY, Wu X, Zhu L, Wang Y (1998) Cloning and characterization of a novel human hepatocyte transcription factor, hB1F, which finds and activates enhancer II of hepatitis B virus. J Biol Chem 273(44):29022–29031

    Article  CAS  PubMed  Google Scholar 

  113. Ishida H, Ueda K, Ohkawa K, Kanazawa Y, Hosui A, Nakanishi F et al (2000) Identification of multiple transcription factors, HLF, FTF, and E4BP4, controlling hepatitis B virus enhancer II. J Virol 74(3):1241–1251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Gilbert S, Galarneau L, Lamontagne A, Roy S, Bélanger L (2000) The hepatitis B virus core promoter is strongly activated by the liver nuclear receptor fetoprotein transcription factor or by ectopically expressed steroidogenic factor 1. J Virol 74(11):5032–5039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Ramiere C, Scholtes C, Diaz O, Icard V, Perrin-Cocon L, Trabaud MA et al (2008) Transactivation of the hepatitis B virus core promoter by the nuclear receptor FXRα. J Virol 82(21):10832–10840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Reese VC, Oropeza CE, McLachlan A (2013) Independent activation of hepatitis B virus biosynthesis by retinoids, peroxisome proliferators, and bile acids. J Virol 87(2):991–997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Reese VC, Ondracek CR, Rushing CN, Li L, Oropeza CE, McLachlan A (2011) Multiple nuclear receptors may regulate hepatitis B virus biosynthesis during development. Int J Biochem Cell Biol 43(2):230–237

    Article  CAS  PubMed  Google Scholar 

  118. Ondracek CR, Reese VC, Rushing CN, Oropeza CE, McLachlan A (2009) Distinct regulation of hepatitis B virus biosynthesis by peroxisome proliferator-activated receptor γ coactivator 1α and small heterodimer partner in human hepatoma cell lines. J Virol 83(23):12545–12551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Lai CK, Ting LP (1999) Transcriptional repression of human hepatitis B virus genes by a bZIP family member, E4BP4. J Virol 73(4):3197–3209

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Raney AK, Johnson JL, Palmer CNA, McLachlan A (1997) Members of the nuclear receptor superfamily regulate transcription from the hepatitis B virus nucleocapsid promoter. J Virol 71(2):1058–1071

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Guo W, Chen M, Yen TSB, Ou J-H (1993) Hepatocyte-specific expression of the hepatitis B virus core promoter depends on both positive and negative regulation. Mol Cell Biol 13:443–448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Johnson JL, Raney AK, McLachlan A (1995) Characterization of a functional hepatocyte nuclear factor 3 binding site in the hepatitis B virus nucleocapsid promoter. Virology 208:147–158

    Article  CAS  PubMed  Google Scholar 

  123. Buckwold VE, Xu ZC, Yen TSB, Ou JH (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

    Article  CAS  PubMed  Google Scholar 

  124. Yu XM, Mertz JE (1997) Differential regulation of the pre-C and pregenomic promoters of human hepatitis B virus by members of the nuclear receptor superfamily. J Virol 71:9366–9374

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Ondracek CR, Rushing CN, Reese VC, Oropeza CE, McLachlan A (2009) Peroxisome proliferator-activated receptor γ coactivator 1α and small heterodimer partner differentially regulate nuclear receptor-dependent hepatitis B virus biosynthesis. J Virol 83(23):12535–12544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Chen I-H, Huang C-J, Ting L-P (1995) Overlapping initiator and TATA box functions in the basal core promoter of hepatitis B virus. J Virol 69:3647–3657

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Garcia AD, Ostapchuk P, Hearing P (1993) Functional interaction of nuclear factors EF-C, HNF-4, and RXRα with hepatitis B virus enhancer I. J Virol 67:3940–3950

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Huan B, Siddiqui A (1992) Retinoid X receptor RXRα binds to and trans-activates the hepatitis B virus enhancer. Proc Natl Acad Sci USA 89:9059–9063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Raney AK, Easton AJ, Milich DR, McLachlan A (1991) Promoter-specific transactivation of hepatitis B virus transcription by a glutamine- and proline-rich domain of hepatocyte nuclear factor 1. J Virol 65:5774–5781

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Chang H-K, Wang B-Y, Yuh C-H, Wei C-L, Ting L-P (1989) A liver-specific nuclear factor interacts with the promoter region of the large surface protein gene of human hepatitis B virus. Mol Cell Biol 9:5189–5197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Raney AK, Zhang P, McLachlan A (1995) Regulation of transcription from the hepatitits B virus large surface antigen promoter by hepatocyte nuclear factor 3. J Virol 69:3265–3272

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Raney AK, McLachlan A (1995) Characterization of the hepatitis B virus large surface antigen promoter Sp1 binding site. Virology 208:399–404

    Article  CAS  PubMed  Google Scholar 

  133. Raney AK, Easton AJ, McLachlan A (1994) Characterization of the minimal elements of the hepatitis B virus large surface antigen promoter. J Gen Virol 75:2671–2679

    Article  CAS  PubMed  Google Scholar 

  134. 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

    Article  CAS  PubMed  Google Scholar 

  135. Santoro C, Mermod N, Andrews PC, Tjian R (1988) A family of human CCAAT-box-binding proteins active in transcription and DNA replication: cloning and expression of multiple cDNAs. Nature 334:218–224

    Article  CAS  PubMed  Google Scholar 

  136. Shaul Y, Ben Levy R, De Medina T (1986) High affinity binding site for nuclear factor I next to the hepatitis B virus S gene promoter. EMBO J 5:1967–1971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Raney AK, Le HB, McLachlan A (1992) Regulation of transcription from the hepatitis B virus major surface antigen promoter by the Sp1 transcription factor. J Virol 66:6912–6921

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Lu CC, Yen TSB (1996) Activation of the hepatitis B virus S promoter by transcription factor NF-Y via a CCAAT element. Virology 225:387–394

    Article  CAS  PubMed  Google Scholar 

  139. Landschulz WH, Johnson PF, Adashi EY, Graves BJ, McKnight SL (1988) Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev 2:786–800

    Article  CAS  PubMed  Google Scholar 

  140. Ori A, Zauberman A, Doitsh G, Paran N, Oren M, Shaul Y (1998) p53 binds and represses the HBV enhancer: an adjacent enhancer element can reverse the transcription effect of p53. EMBO J 17(2):544–553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Nakao K, Nakata K, Yamashita M, Tamada Y, Hamasaki K, Ishikawa H et al (1999) p48 (ISGF-3gamma) is involved in interferon-α-induced suppression of hepatitis B virus enhancer-1 activity. J Biol Chem 274(40):28075–28078

    Article  CAS  PubMed  Google Scholar 

  142. Patel NU, Jameel S, Isom H, Siddiqui A (1989) Interactions between nuclear factors and the hepatitis B virus enhancer. J Virol 63:5293–5301

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Ben-Levy R, Faktor O, Berger I, Shaul Y (1989) Cellular factors that interact with the hepatitis B virus enhancer. Mol Cell Biol 9:1804–1809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Chen M, Hieng S, Qian X, Costa R, Ou JH (1994) Regulation of hepatitis B virus ENI activity by hepatocyte-enriched transcription factor HNF3. Virology 205:127–132

    Article  CAS  PubMed  Google Scholar 

  145. Ori A, Shaul Y (1995) Hepatitis B virus enhancer binds and is activated by the hepatocyte nuclear factor 3. Virology 207:98–106

    Article  CAS  PubMed  Google Scholar 

  146. Huan B, Kosovsky MJ, Siddiqui A (1995) Retinoid X receptor α transactivates the hepatitis B virus enhancer 1 element by forming a heterodimeric complex with the peroxisome proliferator-activated receptor. J Virol 69:547–551

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Siegrist CA, Durand B, Emery P, David E, Hearing P, Mach B et al (1993) RFX1 is identical to enhancer factor C and functions as a transactivator of the hepatitis B virus enhancer. Mol Cell Biol 13:6375–6384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Ostapchuk P, Scheirle G, Hearing P (1989) Binding of nuclear factor EF-C to a functional domain of the hepatitis B virus enhancer region. Mol Cell Biol 9:2787–2797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Maguire HF, Hoeffler JP, Siddiqui A (1991) HBV X protein alters the DNA binding specificity of CREB and ATF-2 by protein-protein interactions. Science 252:842–844

    Article  CAS  PubMed  Google Scholar 

  150. Zhang P, McLachlan A (1994) Differentiation-specific transcriptional regulation of the hepatitis B virus nucleocapsid gene in human hepatoma cell lines. Virology 202:430–440

    Article  CAS  PubMed  Google Scholar 

  151. Antonucci TK, Rutter WJ (1989) Hepatitis B virus (HBV) promoters are regulated by the HBV enhancer in a tissue-specific manner. J Virol 63:579–583

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Lo W-Y, Ting L-P (1994) Repression of enhancer II activity by a negative regulatory element in the hepatitis B virus genome. J Virol 68:1758–1764

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Doitsh G, Shaul Y (2004) Enhancer I predominance in hepatitis B virus gene expression. Mol Cell Biol 24(4):1799–1808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Faktor O, Budlovsky S, Ben Levy R, Shaul Y (1990) A single element within the hepatitis B virus enhancer binds multiple proteins and responds to multiple stimuli. J Virol 64:1861–1863

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Shaul Y, Ben Levy R (1987) Multiple nuclear proteins in liver cells are bound to hepatitis B virus enhancer element and its upstream sequences. EMBO J 6:1913–1920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Shaul Y, Rutter WJ, Laub O (1985) A human hepatitis B viral enhancer element. EMBO J 4:427–430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Trujillo MA, Letovsky J, Maguire HF, Lopez-Cabrera M, Siddiqui A (1991) Functional analysis of a liver-specific enhancer of the hepatitis B virus. Proc Natl Acad Sci USA 88:3797–3801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Bulla GA, Siddiqui A (1988) The hepatitis B virus enhancer modulates transcription of the hepatitis B virus surface antigen gene from an internal location. J Virol 62:1437–1441

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Jameel S, Siddiqui A (1986) The human hepatitis B virus enhancer requires trans-acting cellular factor(s) for activity. Mol Cell Biol 6:710–715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Guo W, Bell KD, Ou J-H (1991) Characterization of the hepatitis B virus EnhI enhancer and X promoter complex. J Virol 65:6686–6692

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Yuh C-H, Ting L-P (1993) Differentiated liver cell specificity of the second enhancer of hepatitis B virus. J Virol 67:142–149

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Yuh C-H, Ting L-P (1990) The genome of hepatitis B virus contains a second enhancer: cooperation of two elements within this enhancer is required for its function. J Virol 64:4281–4287

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Wang Y, Chen P, Wu X, Sun A-L, Wang H, Zhu Y-A et al (1990) A new enhancer element, ENII, identified in the X gene of hepatitis B virus. J Virol 64:3977–3981

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Vannice JL, Levinson AD (1988) Properties of the human hepatitis B virus enhancer: position effects and cell-type nonspecificity. J Virol 62:1305–1313

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Raney AK, Milich DR, McLachlan A (1989) Characterization of hepatitis B virus major surface antigen gene transcriptional regulatory elements in differentiated hepatoma cell lines. J Virol 63:3919–3925

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Raney AK, Milich DR, Easton AJ, McLachlan A (1990) Differentiation specific transcriptional regulation of the hepatitis B virus large surface antigen gene in human hepatoma cell lines. J Virol 64:2360–2368

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Zhang P, Raney AK, McLachlan A (1992) Characterization of the hepatitis B virus X- and nucleocapsid gene transcriptional regulatory elements. Virology 191:31–41

    Article  CAS  PubMed  Google Scholar 

  168. Tognoni A, Cattaneo R, Serfling E, Schaffner W (1985) A novel expression selection approach allows precise mapping of the hepatitis B virus enhancer. Nucleic Acids Res 13:7457–7472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Ou J-H, Rutter WJ (1987) Regulation of secretion of the hepatitis B virus major surface antigen by the preS-1 protein. J Virol 61:782–786

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Karpen S, Banerjee R, Zelent A, Price P, Acs G (1988) Identification of protein-binding sites in the hepatitis B virus enhancer and core promoter domains. Mol Cell Biol 8:5159–5165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Yee J-K (1989) A liver-specific enhancer in the core promoter region of human hepatitis B virus. Science 246:658–661

    Article  CAS  PubMed  Google Scholar 

  172. Raney AK, Milich DR, McLachlan A (1991) Complex regulation of transcription from the hepatitis B virus major surface antigen promoter in human hepatoma cell lines. J Virol 65:4805–4811

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Chang HK, Chou CK, Chang C, Su TS, Hu C, Yoshida M et al (1987) The enhancer sequence of human hepatitis B virus can enhance the activity of its surface gene promoter. Nucleic Acids Res 15:2261–2268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. De-Medina T, Faktor O, Shaul Y (1988) The S promoter of hepatitis B virus is regulated by positive and negative elements. Mol Cell Biol 8:2449–2455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Faktor O, De Medina T, Shaul Y (1988) Regulation of hepatitis B virus S gene promoter in transfected cell lines. Virology 162:362–368

    Article  CAS  PubMed  Google Scholar 

  176. Pourcel C, Louis A, Gervais M, Chenciner N, Dubois M-F, Tiollais P (1982) Transcription of the hepatitis B surface antigen gene in mouse cells transformed with cloned viral DNA. J Virol 42:100–105

    CAS  PubMed  PubMed Central  Google Scholar 

  177. Nakao K, Miyao Y, Ohe Y, Tamaoki T (1989) Involvement of an AFP1-binding site in cell-specific transcription of the pre-S1 region of the human hepatitis B virus surface antigen gene. Nucleic Acids Res 17:9833–9842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. López-Cabrera M, Letovsky J, Hu K-Q, Siddiqui A (1990) Multiple liver-specific factors bind to the hepatitis B virus core/pregenomic promoter: trans-activation and repression by CCAAT/enhancer binding protein. Proc Natl Acad Sci USA 87:5069–5073

    Article  PubMed  PubMed Central  Google Scholar 

  179. Waisman A, Aloni Y, Laub O (1990) In vitro regulation of human hepatitis B virus core gene transcription. Virology 177:737–744

    Article  CAS  PubMed  Google Scholar 

  180. Yaginuma K, Koike K (1989) Identification of a promoter region for 3.6-kilobase mRNA of hepatitis B virus and specific cellular binding protein. J Virol 63:2914–2920

    CAS  PubMed  PubMed Central  Google Scholar 

  181. Kosovsky MJ, Huan BF, Siddiqui A (1996) Purification and properties of rat liver nuclear proteins that interact with the hepatitis B virus enhancer 1. J Biol Chem 271:21859–21869

    Article  CAS  PubMed  Google Scholar 

  182. Zhou D-X, Yen TSB (1991) The ubiquitous transcription factor Oct-1 and the liver- specific factor HNF-1 are both required to activate transcription of a hepatitis B virus promoter. Mol Cell Biol 11:1353–1359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Dikstein R, Faktor O, Shaul Y (1990) Hierarchic and cooperative binding of the rat liver nuclear protein C/EBP at the hepatitis B virus enhancer. Mol Cell Biol 10:4427–4430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. López-Cabrera M, Letovsky J, Hu K-Q, Siddiqui A (1991) Transcriptional factor C/EBP binds to and transactivates the enhancer element II of the hepatitis B virus. Virology 183:825–829

    Article  PubMed  Google Scholar 

  185. Yuh C-H, Chang Y-L, Ting L-P (1992) Transcriptional regulation of precore and pregenomic RNAs of hepatitis B virus. J Virol 66:4073–4084

    CAS  PubMed  PubMed Central  Google Scholar 

  186. Li M, Xie YH, Wu X, Kong YY, Wang Y (1995) HNF3 binds and activates the second enhancer, ENII, of hepatitis B virus. Virology 214:371–378

    Article  CAS  PubMed  Google Scholar 

  187. Pei D, Shih C (1990) Transcriptional activation and repression by cellular DNA-binding protein C/EBP. J Virol 64:1517–1522

    CAS  PubMed  PubMed Central  Google Scholar 

  188. Sells MA, Chen M-L, Acs G (1987) Production of hepatitis B virus particles in HepG2 cells transfected with cloned hepatitis B virus DNA. Proc Natl Acad Sci USA 84:1005–1009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Tang H, McLachlan A (2001) Transcriptional regulation of hepatitis B virus by nuclear hormone receptors is a critical determinant of viral tropism. Proc Natl Acad Sci USA 98:1841–1846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Junker M, Galle P, Schaller H (1987) Expression and replication of the hepatitis B virus genome under foreign promoter control. Nucleic Acids Res 15:10117–10132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Tang H, McLachlan A (2002) Mechanisms of inhibition of nuclear hormone receptor dependent hepatitis B virus replication by hepatocyte nuclear factor 3β. J Virol 76:8572–8581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Raney AK, Kline EF, Tang H, McLachlan A (2001) Transcription and replication of a natural hepatitis B virus nucleocapsid promoter variant is reguated in vivo by peroxisome proliferators. Virology 289:239–251

    Article  CAS  PubMed  Google Scholar 

  193. Guidotti LG, Eggers CM, Raney AK, Chi SY, Peters JM, Gonzalez FJ et al (1999) In vivo regulation of hepatitis B virus replication by peroxisome proliferators. J Virol 73(12):10377–10386

    CAS  PubMed  PubMed Central  Google Scholar 

  194. Oropeza CE, Li L, McLachlan A (2008) Differential inhibition of nuclear hormone receptor dependent hepatitis B virus replication by small heterodimer partner. J Virol 82(8):3814–3821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Li L, Oropeza CE, Sainz B, Uprichard SL, Gonzalez FJ, McLachlan A (2009) Developmental regulation of hepatitis B virus biosynthesis by hepatocyte nuclear factor 4α. PLoS One 4(5):e5489

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  196. Reese VC, Moore DD, McLachlan A (2012) Limited effects of bile acids and small heterodimer partner on hepatitis B virus biosynthesis in vivo. J Virol 86(5):2760–2768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Kyrmizi I, Hatzis P, Katrakili N, Tronche F, Gonzalez FJ, Talianidis I (2006) Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev 20(16):2293–2305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Li L, Oropeza CE, Kaestner KH, McLachlan A (2009) Limited effects of fasting on hepatitis B virus (HBV) biosynthesis in HBV transgenic mice. J Virol 83(4):1682–1688

    Article  CAS  PubMed  Google Scholar 

  199. Ondracek CR, McLachlan A (2011) Role of peroxisome proliferator-activated receptor gamma coactivator 1α in AKT/PKB-mediated inhibition of hepatitis B virus biosynthesis. J Virol 85(22):11891–11900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Shalaby RE, Iram S, Çakal B, Oropeza CE, McLachlan A (2017) PGC1α transcriptional adaptor function governs hepatitis B virus replication by controlling HBcAg/p21 protein-mediated capsid formation. J Virol 91(20):e00790-17

    Article  PubMed  PubMed Central  Google Scholar 

  201. Shlomai A, Paran N, Shaul Y (2006) PGC-1α controls hepatitis B virus through nutritional signals. Proc Natl Acad Sci USA 103(43):16003–16008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Seifer M, Zhou S, Standring DN (1993) A micromolar pool of antigenically distinct precursors is required to initiate cooperative assembly of hepatitis B virus capsids in Xenopus oocytes. J Virol 67:249–257

    CAS  PubMed  PubMed Central  Google Scholar 

  203. Porterfield JZ, Dhason MS, Loeb DD, Nassal M, Stray SJ, Zlotnick A (2010) Full-length hepatitis B virus core protein packages viral and heterologous RNA with similarly high levels of cooperativity. J Virol 84(14):7174–7184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Shlomai A, Shaul Y (2008) The “metabolovirus” model of hepatitis B virus suggests nutritional therapy as an effective anti-viral weapon. Med Hypotheses 71(1):53–57

    Article  PubMed  Google Scholar 

  205. Rhee J, Inoue Y, Yoon JC, Puigserver P, Fan ML, Gonzalez FJ et al (2003) Regulation of hepatic fasting response by PPARγ coactivator-1α (PGC-1): requirement for hepatocyte nuclear factor 4α in gluconeogenesis. Proc Natl Acad Sci USA 100(7):4012–4017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Puigserver P, Spiegelman BM (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α): transcriptional coactivator and metabolic regulator. Endocr Rev 24(1):78–90

    Article  CAS  PubMed  Google Scholar 

  207. Lin J, Handschin C, Spiegelman BM (2005) Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 1(6):361–370

    Article  PubMed  CAS  Google Scholar 

  208. Yoon JC, Puigserver P, Chen GX, Donovan J, Wu ZD, Rhee J et al (2001) Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413(6852):131–138

    Article  CAS  PubMed  Google Scholar 

  209. Wang L, Lee YK, Bundman D, Han Y, Thevananther S, Kim CS et al (2002) Redundant pathways for negative feedback regulation of bile acid production. Dev Cell 2(6):721–731

    Article  CAS  PubMed  Google Scholar 

  210. Goodwin B, Jones SA, Price RR, Watson MA, McKee DD, Moore LB et al (2000) A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell 6(3):517–526

    Article  CAS  PubMed  Google Scholar 

  211. Lu TT, Makishima M, Repa JJ, Schoonjans K, Kerr TA, Auwerx J et al (2000) Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell 6(3):507–515

    Article  CAS  PubMed  Google Scholar 

  212. Komiya Y, Katayama K, Yugi H, Mizui M, Matsukura H, Tomoguri T et al (2008) Minimum infectious dose of hepatitis B virus in chimpanzees and difference in the dynamics of viremia between genotype A and genotype C. Transfusion 48(2):286–294

    PubMed  Google Scholar 

  213. Barker LF, Chisari FV, McGrath PP, Dalgard DW, Kirschstein RL, Almeida JD et al (1973) Transmission of type B viral hepatitis to chimpanzees. J Infect Dis 127:648–662

    Article  CAS  PubMed  Google Scholar 

  214. Walter E, Keist R, Niederöst B, Pult I, Blum HE (1996) Hepatitis B virus infection of tupaia hepatocytes in vitro and in vivo. Hepatology 24(1):1–5

    CAS  PubMed  Google Scholar 

  215. Yan RQ, Su JJ, Huang DR, Gan YC, Yang C, Huang GH (1996) Human hepatitis B virus and hepatocellular carcinoma. I. Experimental infection of tree shrews with hepatitis B virus. J Cancer Res Clin Oncol 122(5):283–288

    Article  CAS  PubMed  Google Scholar 

  216. Tang H, McLachlan A (2002) Avian and mammalian hepadnaviruses have distinct transcription factor requirements for viral replication. J Virol 76(15):7468–7472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Summers J, Smolec JM, Snyder R (1978) A virus similar to human hepatitis B virus associated with hepatitis and hepatoma in woodchucks. Proc Natl Acad Sci USA 75:4533–4537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. Mason WS, Seal G, Summers J (1980) Virus of Pekin ducks with structural and biological relatedness to human hepatitis B virus. J Virol 36:829–836

    CAS  PubMed  PubMed Central  Google Scholar 

  219. Chisari FV (1995) Hepatitis B virus transgenic mice: insights into the virus and the disease. Hepatology 22:1316–1325

    CAS  PubMed  Google Scholar 

  220. McFadden VC, Shalaby RE, Iram S, Oropeza CE, Landolfi JA, Lyubimov AV et al (2017) Hepatic deficiency of the pioneer transcription factor FoxA restricts hepatitis B virus biosynthesis by the developmental regulation of viral DNA methylation. PLoS Pathog 13(2):e1006239

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  221. Bruss V, Ganem D (1991) The role of envelope proteins in hepatitis B virus assembly. Proc Natl Acad Sci USA 88:1059–1063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Anderson AL, Banks KE, Pontoglio M, Yaniv M, McLachlan A (2005) Alpha/beta interferon differentially modulates the clearance of cytoplasmic encapsidated replication intermediates and nuclear covalently closed circular hepatitis B virus (HBV) DNA from the livers of hepatocyte nuclear factor 1{alpha}-null HBV transgenic mice. J Virol 79(17):11045–11052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Chang HK, Wang BY, Yuh CH, Wei CL, Ting LP (1989) A liver-specific nuclear factor interacts with the promoter region of the large surface protein gene of human hepatitis B virus. Mol Cell Biol 9(11):5189–5197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Summers J, Smith PM, Horwich AL (1990) Hepadnavirus envelope proteins regulate covalently closed circular DNA amplification. J Virol 64:2819–2824

    CAS  PubMed  PubMed Central  Google Scholar 

  225. Peters JM, Shah YM, Gonzalez FJ (2012) The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention. Nat Rev Cancer 12:181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  226. Peraza MA, Burdick AD, Marin HE, Gonzalez FJ, Peters JM (2006) The toxicology of ligands for peroxisome proliferator-activated receptors (PPAR). Toxicol Sci 90(2):269–295

    Article  CAS  PubMed  Google Scholar 

  227. Li L, Oropeza CE, Sainz B Jr, Uprichard SL, Gonzalez FJ, McLachlan A (2009) Developmental regulation of hepatitis B virus biosynthesis by hepatocyte nuclear factor 4α. PLoS One 4(5):e5489

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  228. Banks KE, Anderson AL, Tang H, Hughes DE, Costa RH, McLachlan A (2002) Hepatocyte nuclear factor 3β inhibits hepatitis B virus replication in vivo. J Virol 76:12974–12980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Li Z, White P, Tuteja G, Rubins N, Sackett S, Kaestner KH (2009) Foxa1 and Foxa2 regulate bile duct development in mice. J Clin Invest 119(6):1537–1545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. Wu X, Zhang Y (2017) TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet 18:517

    Article  CAS  PubMed  Google Scholar 

  231. Gao S, Duan Z-P, Coffin CS (2015) Clinical relevance of hepatitis B virus variants. World J Hepatol 7(8):1086–1096

    Article  PubMed  PubMed Central  Google Scholar 

  232. Glebe D, Geipel A (2014) Selected phenotypic assays used to evaluate antiviral resistance and viral fitness of hepatitis B virus and its variants. Intervirology 57(3–4):225–231

    Article  CAS  PubMed  Google Scholar 

  233. Li L, Chirapu SR, Finn MG, Zlotnick A (2013) Phase diagrams map the properties of antiviral agents directed against hepatitis B virus Core assembly. Antimicrob Agents Chemother 57(3):1505–1508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Venkatakrishnan B, Katen SP, Francis S, Chirapu S, Finn MG, Zlotnick A (2016) Hepatitis B virus capsids have diverse structural responses to small-molecule ligands bound to the heteroaryldihydropyrimidine pocket. J Virol 90(8):3994–4004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Deres K, Schröder CH, Paessens A, Goldmann S, Hacker HJ, Weber O et al (2003) Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids. Science 299(5608):893–896

    Article  CAS  PubMed  Google Scholar 

  236. Cho MH, Jeong H, Kim YS, Kim JW, Jung G (2014) 2-amino-N-(2,6-dichloropyridin-3-yl)acetamide derivatives as a novel class of HBV capsid assembly inhibitor. J Viral Hepat 21(12):843–852

    Article  CAS  PubMed  Google Scholar 

  237. Campagna MR, Liu F, Mao R, Mills C, Cai D, Guo F et al (2013) Sulfamoylbenzamide derivatives inhibit the assembly of hepatitis B virus nucleocapsids. J Virol 87(12):6931–6942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  238. Wu S, Zhao Q, Zhang P, Kulp J, Hu L, Hwang N et al (2017) Discovery and mechanistic study of benzamide derivatives that modulate hepatitis B virus capsid assembly. J Virol 91(16):e00519-17

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by Public Health Service grant AI125401 from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA

    Claudia E. Oropeza, Grant Tarnow, Abhayavarshini Sridhar, Taha Y. Taha, Rasha E. Shalaby & Alan McLachlan

  2. Department of Microbiology and Immunology, Faculty of Medicine, Tanta University, Egypt, Egypt

    Rasha E. Shalaby

Authors
  1. Claudia E. Oropeza
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  2. Grant Tarnow
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  3. Abhayavarshini Sridhar
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  4. Taha Y. Taha
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  5. Rasha E. Shalaby
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  6. Alan McLachlan
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Corresponding author

Correspondence to Alan McLachlan .

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Editors and Affiliations

  1. Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China

    Hong Tang

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Oropeza, C.E., Tarnow, G., Sridhar, A., Taha, T.Y., Shalaby, R.E., McLachlan, A. (2020). The Regulation of HBV Transcription and Replication. In: Tang, H. (eds) Hepatitis B Virus Infection. Advances in Experimental Medicine and Biology, vol 1179. Springer, Singapore. https://doi.org/10.1007/978-981-13-9151-4_3

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