Skip to main content
SpringerLink
Log in

Transcriptional Control of Hepadnavirus Gene Expression

  • Chapter
Hepadnaviruses

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 168))

Abstract

Hepadnaviruses multiply their DNA genome by reverse transcription of an RNA intermediate, termed pregenomic RNA. Therefore, hepadnaviral transcription has a dual function: the production of the RNA template for genome replication and the synthesis of messenger RNAs (mRNAs). The very small viral genome is fully covered by extensively overlapping coding sequences, requiring an expression strategy that uses differential transcription initiation and unspliced transcripts to produce at least seven viral gene products from four open reading frames. This complex organization implies that the hepatitis B virus (HBV) genome contains several transcriptional control regions, that these regions are located at short distances from each other (maximally 1.6 kb apart in the circular 3.2-kb genome), and that all are themselves actively transcribed during viral replication and eventually translated into protein. This scenario, which is without precedent in other known replication units, has most likely imposed unusual restrictions on the evolution of the mechanisms regulating hepadnaviral gene expression and hence on elements involved in transcriptional control.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adhya S, Gottesman M (1982) Promoter occlusion transcription through a promoter may inhibit its activity Cell 29: 939–944

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Araki K, Miyazaki JI, Hino O, Tomita N, Chisaka O, Matsubara K, Yamamura KI (1989) Expression and replication of hepatitis B virus genome in transgenic mice. Proc Natl Acad Sci USA 86: 207–211

    Article  PubMed  CAS  Google Scholar 

  • Aufiero B, Schneider RJ (1990) The hepatitis B virus X-gene product transactivates both RNA polymerase II and III promoters. EMBO J 9: 497–504

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Brunetto MR, Stemler M, Bonino F, Schödel F, Oliveri F, Rizzetto M, Verme G, Will H (1990) A new hepatitis B virus strain in patients with severe anti-HBc positive chronic hepatitis. J Hepatol 10:258–261

    Article  PubMed  CAS  Google Scholar 

  • Bulla G, Siidiqui 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

    PubMed  CAS  Google Scholar 

  • Büscher M, Reiser W, Will H, Schaller H (1985) Transcripts and the putative RNA pregenome of duck hepatitis B virus implications for reverse transcription. Cell 40: 717–724

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  • Chang C, Enders G, Sprengel R, Peters N, Varmus HE, Ganem D (1987) Expression of the precore region of an avian hepatitis B virus is not required for viral replication. J Virol 61: 3322–3325

    PubMed  CAS  Google Scholar 

  • Chang LJ, Ganem D, Varmus HE (1990) Mechanism of translation of the hepadnaviral polymerase (P) gene. Proc Natl Acad Sci USA 87: 5158–5162

    Article  PubMed  CAS  Google Scholar 

  • Chen PJ, Chen CR, Sung JL, Chen DS (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

    PubMed  CAS  Google Scholar 

  • Colgrove R, Simon G, Ganem D (1989) Transcriptional of homologous and heterologous genes by the hepadnaviral X gene product in cells permissive for viral replication. J Virol 63: 4019–4026

    PubMed  CAS  Google Scholar 

  • Courtois G, Baumhueter S, Crabtree GR (1988) Purified hepatocyte nuclear factor 1 interacts with a family of hepatocyte specific promoters. Proc Natl Acad Sci USA 85: 7937–7941

    Article  PubMed  CAS  Google Scholar 

  • Cullen BR, Greene WC (1990) Regulatory pathways governing HIV-1 replication. Cell 58: 423–426

    Article  Google Scholar 

  • 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

    Google Scholar 

  • Enders GH, Ganem D, Varmus H (1985) Mapping the major transcripts of ground squirrel hepatitis virus the presumptive template for reverse transcriptase is terminally redundant. Cell 42: 297–308

    Article  PubMed  CAS  Google Scholar 

  • Faktor O, Shaul Y (1990) The identifcation of hepatitis B virus X gene responsive elements reveals functional similarity of X and HTLV-I tax. Oncogene 6: 867–872

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Fischer M (1987) Protein/DNA Wechselwirkungen am Genom des Enten Hepatitis B Virus (DHBV). Diploma thesis (Diplomarbeit), University of Heidelberg

    Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Ganem D, Varmus HE (1987) The molecular biology of hepatitis B viruses. Annu Rev Biochem 56: 651–693

    Article  PubMed  CAS  Google Scholar 

  • Gough N (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  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Kekule AS, Lauer U, Meyer M, Caselmann WH, Hofschneider PH, Koshy R (1990) The pres2/s region of integrated hepatitis B virus DNA encodes a transcriptional transactivator. Nature 343: 457–461

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Cabrera M, Letovsky J, Hu KQ, Siddiqui A (1990) Multiple liver-specific factors bind to the hepatitis B virus core/pregenomic Trans-activation and repression by CAAT/enhancer binding protein. Proc Natl Acad Sci USA 87: 5069–5073

    Article  PubMed  CAS  Google Scholar 

  • Miller RH, Robinson WS (1986) Common evolutionary origin of hepatitis B viruses and retroviruses. Proc Natl Acad Sci USA 83: 2531–2535

    Article  PubMed  CAS  Google Scholar 

  • Möröy J, Etiemble J, Trepo C, Tiollais P, Buendia MA (1985) Transcription of woodchuck hepatitis virus in the chronically infected liver. EMBO J 4: 1507–1514

    PubMed  Google Scholar 

  • Nakao K, Miyao Y, Ohe Y, Tamaoki T (1989) Involvement of an AFP-1 binding site in cell specific transcription of the pre-SI region of the human hepatitis B virus surface antigen gene. Nucleic Acids Res 17: 9833–9842

    Article  PubMed  CAS  Google Scholar 

  • Nassal M, Junker-Niepmann M, Schaller H (1990) Translation inactivation of RNA function Discrimination against a subset of genomic transcripts during hepatitis B virus nucleocapsid assembly. Cell 63:1357–1363

    Article  PubMed  CAS  Google Scholar 

  • Okamoto H, Yotsumoto S, Akahane Y, Yamanaka T, Miyazaki Y, Sugai Y, Tsuda F, Tanaka T, Miyakawa Y, Mayumi M (1990) Hepatitis 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

    PubMed  CAS  Google Scholar 

  • Ou JH, Yeh CT, Yen TS (1989) Transport of hepatitis B virus precore protein into the nucleus after cleavage of its signal peptide. J Virol 63: 5238–543

    PubMed  CAS  Google Scholar 

  • Pasek M, Goto T, Gilbert W, Zink B, Schaller H, McKay P, Leadbetter G, Murray K (1979) Hepatitis B virus genes and their expression in E. coli. Nature 282: 575–579

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Pfaff E, Salfeld J, Gmelin K, Schaller H, Theilmann L (1987) Synthesis of the X protein of hepatitis B virus in vitro and detection of anti X antibodies in human sera. Virology 158: 456–460

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Priess A (1988) System zur Untersuchung spezifischer Aspekte der 3′-Prozessierung von HBV mRNAs. Diploma thesis (Diplomarbeit), University of Heidelberg

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Russnak R, Ganem D (1990) Sequences 5′ to the polyadenylation signal mediate differential poly(A) site use in hepatitis B viruses. Genes Dev 4: 764–776

    Article  PubMed  CAS  Google Scholar 

  • Saito I, Oya Y, Yamamoto K, Yuasa T, Shimojo H (1985) Construction of nondefective adenovirus type 5 bearing a 2.8-kilobase hepatitis B virus DNA near the right end of its genome. J Virol 54:711–719

    PubMed  CAS  Google Scholar 

  • Schek N, Fischer M, Schaller H (1990) The hepadnaviral X protein in, In: McLachlan A (ed) Molecular biology of hepatitis B viruses, CRC, Boca Raton (CRC Uniscience)

    Google Scholar 

  • Schlicht, HJ, Salfeld J, Schaller H (1987) The preC region of the duck hepatitis B virus is essential to synthesis and secretion of processed core proteins but not for virus formation J Virol 61:3701–3709

    PubMed  CAS  Google Scholar 

  • Shaul Y (1991) Regulation of hepadnavirus transcription. In: McLachlan A (ed) Molecular biology of hepatitis B viruses. CRC, Boca Raton (CRC Uniscience)

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Spandau DF, Lee CH (1988) Trans-activation of viral enhancers by the hepatitis B virus X protein. J Virol 62: 427–434

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Su TS, Lai CJ, Huang JL, Lin LH, Yauk YK, Chang CM, Lo SJ, Han SH (1989) Hepatitis B virus transcript produced by RNA splicing. J Virol 63: 4011–4018

    PubMed  CAS  Google Scholar 

  • Suzuki T, Masui N, Kajino K, Saito I, Miyamura T (1989) Detection and mapping of spliced RNA from a human hepatoma cell line transfected with the hepatitis B virus genome. Proc Natl Acad Sci USA 86: 8422–8426

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Tur-Kaspa R, Burk RD, Shaul Y, Shafritz DA (1986) Hepatitis B virus DNA contains a glucocorticoid-responsive element. Proc Natl Acad Sci USA 83: 1627–1631

    Article  PubMed  CAS  Google Scholar 

  • Tur-Kaspa R, Shaul Y, Moore DD, Burk RD, Okret S, Poellinger L, Shafritz DA (1988) The glucocorticoid receptor recognizes a specific nucleotide sequence in hepatitis B virus DNA causing increased activity of the HBV enhancer. Virology 167: 630–633

    PubMed  CAS  Google Scholar 

  • Twu JS, Robinson WS (1988) Hepatitis B virus X gene can transactivate heterologous viral sequences. Proc Natl Acad Sci USA 86: 2046–2050

    Article  Google Scholar 

  • Twu JS, Schloemer RH (1987) Transcriptional transactivating function of hepatitis B virus. J Virol 61: 3448–3453

    PubMed  CAS  Google Scholar 

  • Twu JS, Schloemer RH (1989) Transcription of the human beta interferon gene is inhibited by hepatitis B virus. J Virol 63: 3065–3071

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Wickens M (1990) How the messenger got its tail addition of poly(A) in the nucleus. Trends Biochem Sci 15:277–281

    Article  PubMed  CAS  Google Scholar 

  • Will H, Reiser W, Weimer T, Pfaff E, Büscher M, Sprengel R, Cattaneo C, Schaller H (1987) Replication strategy of human hepatitis B virus. J Virol 61:904–911

    PubMed  CAS  Google Scholar 

  • Wu JY, Zhou ZY, Judd A, Cartwright CA, Robinson WS (1990) The hepatitis B virus encoded transcriptional trans-activator hbx appears to be a novel protein serine/threonine kinase. Cell 63:687–695

    Article  PubMed  CAS  Google Scholar 

  • 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: 2914–2921

    PubMed  CAS  Google Scholar 

  • 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: 2678–2686

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Zahm P, Hofschneider PH, Koshy R (1988) The HBV X-ORF encodes a transactivator, a potential factor in viral hepatocarcinogenesis. Oncogene 3: 169–177

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Zentrum für Molekulare Biologie, University of Heidelberg, Im Neuenheimer Feld 282, 6900, Heidelberg, Germany

    H. Schaller & M. Fischer

Authors
  1. H. Schaller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA, 19111, USA

    William S. Mason  & Christoph Seeger  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Springer-Verlag Berlin·Heidelberg

About this chapter

Cite this chapter

Schaller, H., Fischer, M. (1991). Transcriptional Control of Hepadnavirus Gene Expression. In: Mason, W.S., Seeger, C. (eds) Hepadnaviruses. Current Topics in Microbiology and Immunology, vol 168. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76015-0_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-76015-0_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-76017-4

  • Online ISBN: 978-3-642-76015-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation