Skip to main content
SpringerLink
Log in

Hepatitis Delta Virus: Virology and Replication

  • Chapter
Hepatitis B Virus in Human Diseases

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

Abstract

The Hepatitis Delta Virus (HDV) is a subviral infectious agent that utilizes the Hepatitis B Virus (HBV) as a helper for propagation. Since HDV infection occurs only in humans infected with HBV, the HDV replication cycle includes that of the helper HBV. The HDV genome is a small circular single stranded RNA similar in structure to plant viroid RNA, which replicates in the cell nucleus through a rolling circle mechanism of RNA synthesis driven by a cellular RNA-dependent RNA polymerase activity. However, unlike plant viroids that do not code for any protein, HDV RNA encodes a protein bearing the hepatitis delta antigen (HDAg), which has no RNA polymerase activity but multiple functions in HDV RNA replication and assembly of core-like ribonucleoproteins (RNPs). HDV RNPs accumulate in the infected cell but can neither bud at a cell membrane nor induce cell membrane lysis for release. Egress of HDV RNPs is dependent upon the assistance of the HBV envelope proteins and their intrinsic capacity to assemble lipoprotein vesicles—or subviral particles—in HBV-infected hepatocytes. Coated with the HBV envelope proteins, the exported HDV virions can survive in the extracellular space and enter HBV-susceptible cells to ensure propagation. Although HDV does not fulfill the criteria for the definition of a virus, it is actually classified as the unique member of the Deltavirus genus. HDV infection is estimated to affect 5–10 % of HBV-infected individuals worldwide, and to cause the most severe form of viral hepatitis and the most difficult to treat.

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 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover 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

Abbreviations

ADAR:

Adenosine deaminase that acts on RNA

AGL:

Antigenic loop

ARMs:

Arginine-rich motifs

Crm1:

Cell region maintenance-1

DHBV:

Duck hepatitis B virus

DIPA:

Delta-interacting protein A

GAG:

Glycosaminoglycan

HBcAg:

HBV core antigen

HBsAg:

Hepatitis B surface antigen

HDAg:

Hepatitis delta antigen

HDV-I:

HDV genotype-I

L-HBsAg:

Large HBsAg

L-HDAg:

Large-HDAg

M-HBsAg:

Middle HBsAg

MVBs:

Multivesicular bodies

NELF:

Negative elongation factor

NES:

Nuclear export signal

NTCP:

Sodium taurocholate cotransporting polypeptide

Pol II:

RNA polymerase II

RdRP:

RNA-dependent RNA polymerase

RNPs:

Ribonucleoproteins

S-HBsAg:

Small HBsAg

S-HDAg:

Small-HDAg

SVPs:

Subviral particles

WHV:

Woodchuck hepatitis virus

WMHBV:

Woolly monkey hepatitis B virus

References

  1. Rizzetto M, Canese MG, Arico S, Crivelli O, Trepo C, Bonino F, et al. Immunofluorescence detection of new antigen-antibody system (delta/anti-delta) associated to hepatitis B virus in liver and in serum of HBsAg carriers. Gut. 1977;18(12):997–1003.

    PubMed Central  CAS  PubMed  Google Scholar 

  2. Bonino F, Heermann KH, Rizzetto M, Gerlich WH. Hepatitis delta virus: protein composition of delta antigen and its hepatitis B virus-derived envelope. J Virol. 1986;58(3):945–50.

    PubMed Central  CAS  PubMed  Google Scholar 

  3. Ponzetto A, Cote PJ, Popper H, Hoyer BH, London WT, Ford EC, et al. Transmission of the hepatitis B virus-associated delta agent to the eastern woodchuck. Proc Natl Acad Sci U S A. 1984;81(7):2208–12.

    PubMed Central  CAS  PubMed  Google Scholar 

  4. Rizzetto M, Canese MG, Gerin JL, London WT, Sly DL, Purcell RH. Transmission of the hepatitis B virus-associated delta antigen to chimpanzees. J Infect Dis. 1980;141(5):590–602.

    CAS  PubMed  Google Scholar 

  5. Denniston KJ, Hoyer BH, Smedile A, Wells FV, Nelson J, Gerin JL. Cloned fragment of the hepatitis delta virus RNA genome: sequence and diagnostic application. Science. 1986;232(4752):873–5.

    CAS  PubMed  Google Scholar 

  6. Wang KS, Choo OL, Weiner AJ, Ou JH, Denniston KJ, Gerin JL, et al. The viroid-like structure of the hepatitis delta (delta) genome: synthesis of a viral antigen in recombinant bacteria. Prog Clin Biol Res. 1987;234:71–82.

    CAS  PubMed  Google Scholar 

  7. Makino S, Chang MF, Shieh CK, Kamahora T, Vannier DM, Govindarajan S, et al. Molecular cloning and sequencing of a human hepatitis delta (delta) virus RNA. Nature. 1987;329(6137):343–6.

    CAS  PubMed  Google Scholar 

  8. Chen PJ, Kalpana G, Goldberg J, Mason W, Werner B, Gerin J, et al. Structure and replication of the genome of the hepatitis delta virus. Proc Natl Acad Sci U S A. 1986;83(22):8774–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  9. Kos A, Dijkema R, Arnberg AC, van der Meide PH, Schellekens H. The hepatitis delta (delta) virus possesses a circular RNA. Nature. 1986;323(6088):558–60.

    CAS  PubMed  Google Scholar 

  10. Ryu WS, Netter HJ, Bayer M, Taylor J. Ribonucleoprotein complexes of hepatitis delta virus. J Virol. 1993;67(6):3281–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  11. Sureau C, Moriarty AM, Thornton GB, Lanford RE. Production of infectious hepatitis delta virus in vitro and neutralization with antibodies directed against hepatitis B virus pre-S antigens. J Virol. 1992;66(2):1241–5.

    PubMed Central  CAS  PubMed  Google Scholar 

  12. Wang CJ, Chen PJ, Wu JC, Patel D, Chen DS. Small-form hepatitis B surface antigen is sufficient to help in the assembly of hepatitis delta virus-like particles. J Virol. 1991;65(12):6630–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Komla-Soukha I, Sureau C. A tryptophan-rich motif in the carboxyl terminus of the small envelope protein of hepatitis B virus is central to the assembly of hepatitis delta virus particles. J Virol. 2006;80(10):4648–55.

    PubMed Central  CAS  PubMed  Google Scholar 

  14. O’Malley B, Lazinski DW. Roles of carboxyl-terminal and farnesylated residues in the functions of the large hepatitis delta antigen. J Virol. 2005;79(2):1142–53.

    PubMed Central  PubMed  Google Scholar 

  15. Sureau C, Guerra B, Lanford RE. Role of the large hepatitis B virus envelope protein in infectivity of the hepatitis delta virion. J Virol. 1993;67(1):366–72.

    PubMed Central  CAS  PubMed  Google Scholar 

  16. Taylor JM. Hepatitis delta virus. Virology. 2006;344(1):71–6.

    CAS  PubMed  Google Scholar 

  17. Koytak ES, Yurdaydin C, Glenn JS. Hepatitis D. Curr Treat Options Gastroenterol. 2007;10(6):456–63.

    PubMed  Google Scholar 

  18. Deny P. Hepatitis delta virus genetic variability: from genotypes I, II, III to eight major clades? Curr Top Microbiol Immunol. 2006;307:151–71.

    CAS  PubMed  Google Scholar 

  19. Cross TJ, Rizzi P, Horner M, Jolly A, Hussain MJ, Smith HM, et al. The increasing prevalence of hepatitis delta virus (HDV) infection in South London. J Med Virol. 2008;80(2):277–82.

    PubMed  Google Scholar 

  20. Wedemeyer H, Heidrich B, Manns MP. Hepatitis D virus infection--not a vanishing disease in Europe! Hepatology. 2007;45(5):1331–2. author reply 2-3.

    PubMed  Google Scholar 

  21. Farci P, Chessa L, Balestrieri C, Serra G, Lai ME. Treatment of chronic hepatitis D. J Viral Hepat. 2007;14 Suppl 1:58–63.

    PubMed  Google Scholar 

  22. Heidrich B, Yurdaydin C, Kabacam G, Ratsch BA, Zachou K, Bremer B, et al. Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta. Hepatology. 2014;60(1):87–97.

    CAS  PubMed  Google Scholar 

  23. Wang KS, Choo QL, Weiner AJ, Ou JH, Najarian RC, Thayer RM, et al. Structure, sequence and expression of the hepatitis delta (delta) viral genome. Nature. 1986;323(6088):508–14.

    CAS  PubMed  Google Scholar 

  24. Griffin BL, Chasovskikh S, Dritschilo A, Casey JL. Hepatitis delta antigen requires a flexible quasi-double-stranded RNA structure to bind and condense hepatitis delta virus RNA in a ribonucleoprotein complex. J Virol. 2014;88(13):7402–11.

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Chang MF, Chen CH, Lin SL, Chen CJ, Chang SC. Functional domains of delta antigens and viral RNA required for RNA packaging of hepatitis delta virus. J Virol. 1995;69(4):2508–14.

    PubMed Central  CAS  PubMed  Google Scholar 

  26. Gudima S, Chang J, Moraleda G, Azvolinsky A, Taylor J. Parameters of human hepatitis delta virus genome replication: the quantity, quality, and intracellular distribution of viral proteins and RNA. J Virol. 2002;76(8):3709–19.

    PubMed Central  CAS  PubMed  Google Scholar 

  27. Defenbaugh DA, Johnson M, Chen R, Zheng YY, Casey JL. Hepatitis delta antigen requires a minimum length of the hepatitis delta virus unbranched rod RNA structure for binding. J Virol. 2009;83(9):4548–56.

    PubMed Central  CAS  PubMed  Google Scholar 

  28. Lin BC, Defenbaugh DA, Casey JL. Multimerization of hepatitis delta antigen is a critical determinant of RNA binding specificity. J Virol. 2010;84(3):1406–13.

    PubMed Central  CAS  PubMed  Google Scholar 

  29. Weiner AJ, Choo QL, Wang KS, Govindarajan S, Redeker AG, Gerin JL, et al. A single antigenomic open reading frame of the hepatitis delta virus encodes the epitope(s) of both hepatitis delta antigen polypeptides p24 delta and p27 delta. J Virol. 1988;62(2):594–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Casey JL. Control of ADAR1 editing of hepatitis delta virus RNAs. Curr Top Microbiol Immunol. 2012;353:123–43.

    PubMed Central  CAS  PubMed  Google Scholar 

  31. Branch AD, Benenfeld BJ, Baroudy BM, Wells FV, Gerin JL, Robertson HD. An ultraviolet-sensitive RNA structural element in a viroid-like domain of the hepatitis delta virus. Science. 1989;243(4891):649–52.

    CAS  PubMed  Google Scholar 

  32. Casey JL, Brown TL, Colan EJ, Wignall FS, Gerin JL. A genotype of hepatitis D virus that occurs in northern South America. Proc Natl Acad Sci U S A. 1993;90(19):9016–20.

    PubMed Central  CAS  PubMed  Google Scholar 

  33. Branch AD, Robertson HD. A replication cycle for viroids and other small infectious RNA’s. Science. 1984;223(4635):450–5.

    CAS  PubMed  Google Scholar 

  34. Kuo MY, Chao M, Taylor J. Initiation of replication of the human hepatitis delta virus genome from cloned DNA: role of delta antigen. J Virol. 1989;63(5):1945–50.

    PubMed Central  CAS  PubMed  Google Scholar 

  35. Wu HN, Lin YJ, Lin FP, Makino S, Chang MF, Lai MM. Human hepatitis delta virus RNA subfragments contain an autocleavage activity. Proc Natl Acad Sci U S A. 1989;86(6):1831–5.

    PubMed Central  CAS  PubMed  Google Scholar 

  36. Sureau C, Taylor J, Chao M, Eichberg JW, Lanford RE. Cloned hepatitis delta virus cDNA is infectious in the chimpanzee. J Virol. 1989;63(10):4292–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  37. Lai MM. The molecular biology of hepatitis delta virus. Annu Rev Biochem. 1995;64:259–86.

    CAS  PubMed  Google Scholar 

  38. Hsieh SY, Chao M, Coates L, Taylor J. Hepatitis delta virus genome replication: a polyadenylated mRNA for delta antigen. J Virol. 1990;64(7):3192–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  39. Cheng J, Kapranov P, Drenkow J, Dike S, Brubaker S, Patel S, et al. Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science. 2005;308(5725):1149–54.

    CAS  PubMed  Google Scholar 

  40. Gudima S, Wu SY, Chiang CM, Moraleda G, Taylor J. Origin of hepatitis delta virus mRNA. J Virol. 2000;74(16):7204–10.

    PubMed Central  CAS  PubMed  Google Scholar 

  41. Modahl LE, Macnaughton TB, Zhu N, Johnson DL, Lai MM. RNA-Dependent replication and transcription of hepatitis delta virus RNA involve distinct cellular RNA polymerases. Mol Cell Biol. 2000;20(16):6030–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  42. Chang J, Nie X, Gudima S, Taylor J. Action of inhibitors on accumulation of processed hepatitis delta virus RNAs. J Virol. 2006;80(7):3205–14.

    PubMed Central  CAS  PubMed  Google Scholar 

  43. Chang J, Nie X, Chang HE, Han Z, Taylor J. Transcription of hepatitis delta virus RNA by RNA polymerase II. J Virol. 2008;82(3):1118–27.

    PubMed Central  CAS  PubMed  Google Scholar 

  44. Huang WH, Chen YS, Chen PJ. Nucleolar targeting of hepatitis delta antigen abolishes its ability to initiate viral antigenomic RNA replication. J Virol. 2008;82(2):692–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  45. Modahl LE, Lai MM. Transcription of hepatitis delta antigen mRNA continues throughout hepatitis delta virus (HDV) replication: a new model of HDV RNA transcription and replication. J Virol. 1998;72(7):5449–56.

    PubMed Central  CAS  PubMed  Google Scholar 

  46. Macnaughton TB, Shi ST, Modahl LE, Lai MM. Rolling circle replication of hepatitis delta virus RNA is carried out by two different cellular RNA polymerases. J Virol. 2002;76(8):3920–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Yamaguchi Y, Filipovska J, Yano K, Furuya A, Inukai N, Narita T, et al. Stimulation of RNA polymerase II elongation by hepatitis delta antigen. Science. 2001;293(5527):124–7.

    CAS  PubMed  Google Scholar 

  48. Yamaguchi Y, Mura T, Chanarat S, Okamoto S, Handa H. Hepatitis delta antigen binds to the clamp of RNA polymerase II and affects transcriptional fidelity. Genes Cells. 2007;12(7):863–75.

    CAS  PubMed  Google Scholar 

  49. Lehmann E, Brueckner F, Cramer P. Molecular basis of RNA-dependent RNA polymerase II activity. Nature. 2007;450(7168):445–9.

    CAS  PubMed  Google Scholar 

  50. Abrahem A, Pelchat M. Formation of an RNA polymerase II preinitiation complex on an RNA promoter derived from the hepatitis delta virus RNA genome. Nucleic Acids Res. 2008;36(16):5201–11.

    PubMed Central  CAS  PubMed  Google Scholar 

  51. Beard MR, MacNaughton TB, Gowans EJ. Identification and characterization of a hepatitis delta virus RNA transcriptional promoter. J Virol. 1996;70(8):4986–95.

    PubMed Central  CAS  PubMed  Google Scholar 

  52. Macnaughton TB, Lai MM. Identification of promoters of hepatitis delta virus RNA transcription on hepatitis delta virus cDNA. Prog Clin Biol Res. 1993;382:13–20.

    CAS  PubMed  Google Scholar 

  53. Haussecker D, Cao D, Huang Y, Parameswaran P, Fire AZ, Kay MA. Capped small RNAs and MOV10 in human hepatitis delta virus replication. Nat Struct Mol Biol. 2008;15(7):714–21.

    PubMed Central  CAS  PubMed  Google Scholar 

  54. Ferre-D’Amare AR, Zhou K, Doudna JA. Crystal structure of a hepatitis delta virus ribozyme. Nature. 1998;395(6702):567–74.

    PubMed  Google Scholar 

  55. Ke A, Ding F, Batchelor JD, Doudna JA. Structural roles of monovalent cations in the HDV ribozyme. Structure. 2007;15(3):281–7.

    CAS  PubMed  Google Scholar 

  56. Riccitelli N, Luptak A. HDV family of self-cleaving ribozymes. Prog Mol Biol Transl Sci. 2013;120:123–71.

    CAS  PubMed  Google Scholar 

  57. Brown AL, Perrotta AT, Wadkins TS, Been MD. The poly(A) site sequence in HDV RNA alters both extent and rate of self-cleavage of the antigenomic ribozyme. Nucleic Acids Res. 2008;36(9):2990–3000.

    PubMed Central  CAS  PubMed  Google Scholar 

  58. Webb CH, Riccitelli NJ, Ruminski DJ, Luptak A. Widespread occurrence of self-cleaving ribozymes. Science. 2009;326(5955):953.

    PubMed Central  CAS  PubMed  Google Scholar 

  59. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495(7441):333–8.

    CAS  PubMed  Google Scholar 

  60. Taylor JM. Host RNA, circles and the origin of hepatitis delta virus. World J Gastroenterol. 2014;20(11):2971–8.

    PubMed Central  PubMed  Google Scholar 

  61. Brazas R, Ganem D. A cellular homolog of hepatitis delta antigen: implications for viral replication and evolution. Science. 1996;274(5284):90–4.

    CAS  PubMed  Google Scholar 

  62. Salehi-Ashtiani K, Luptak A, Litovchick A, Szostak JW. A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene. Science. 2006;313(5794):1788–92.

    CAS  PubMed  Google Scholar 

  63. Chao M, Hsieh SY, Taylor J. Role of two forms of hepatitis delta virus antigen: evidence for a mechanism of self-limiting genome replication. J Virol. 1990;64(10):5066–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  64. Lee CZ, Chen PJ, Chen DS. Large hepatitis delta antigen in packaging and replication inhibition: role of the carboxyl-terminal 19 amino acids and amino-terminal sequences. J Virol. 1995;69(9):5332–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  65. Luo GX, Chao M, Hsieh SY, Sureau C, Nishikura K, Taylor J. A specific base transition occurs on replicating hepatitis delta virus RNA. J Virol. 1990;64(3):1021–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  66. Casey JL, Bergmann KF, Brown TL, Gerin JL. Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism. Proc Natl Acad Sci U S A. 1992;89(15):7149–53.

    PubMed Central  CAS  PubMed  Google Scholar 

  67. Jayan GC, Casey JL. Inhibition of hepatitis delta virus RNA editing by short inhibitory RNA-mediated knockdown of ADAR1 but not ADAR2 expression. J Virol. 2002;76(23):12399–404.

    PubMed Central  CAS  PubMed  Google Scholar 

  68. Wong SK, Lazinski DW. Replicating hepatitis delta virus RNA is edited in the nucleus by the small form of ADAR1. Proc Natl Acad Sci U S A. 2002;99(23):15118–23.

    PubMed Central  CAS  PubMed  Google Scholar 

  69. Casey JL, Tennant BC, Gerin JL. Genetic changes in hepatitis delta virus from acutely and chronically infected woodchucks. J Virol. 2006;80(13):6469–77.

    PubMed Central  CAS  PubMed  Google Scholar 

  70. Huang WH, Chen CW, Wu HL, Chen PJ. Post-translational modification of delta antigen of hepatitis D virus. Curr Top Microbiol Immunol. 2006;307:91–112.

    CAS  PubMed  Google Scholar 

  71. Tseng CH, Jeng KS, Lai MM. Transcription of subgenomic mRNA of hepatitis delta virus requires a modified hepatitis delta antigen that is distinct from antigenomic RNA synthesis. J Virol. 2008;82(19):9409–16.

    PubMed Central  CAS  PubMed  Google Scholar 

  72. Li YJ, Stallcup MR, Lai MM. Hepatitis delta virus antigen is methylated at arginine residues, and methylation regulates subcellular localization and RNA replication. J Virol. 2004;78(23):13325–34.

    PubMed Central  CAS  PubMed  Google Scholar 

  73. Mu JJ, Tsay YG, Juan LJ, Fu TF, Huang WH, Chen DS, et al. The small delta antigen of hepatitis delta virus is an acetylated protein and acetylation of lysine 72 may influence its cellular localization and viral RNA synthesis. Virology. 2004;319(1):60–70.

    CAS  PubMed  Google Scholar 

  74. Hong SY, Chen PJ. Phosphorylation of serine 177 of the small hepatitis delta antigen regulates viral antigenomic RNA replication by interacting with the processive RNA polymerase II. J Virol. 2010;84(3):1430–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  75. Tseng CH, Cheng TS, Shu CY, Jeng KS, Lai MM. Modification of small hepatitis delta virus antigen by SUMO protein. J Virol. 2010;84(2):918–27.

    PubMed Central  CAS  PubMed  Google Scholar 

  76. Macnaughton TB, Lai MM. Genomic but not antigenomic hepatitis delta virus RNA is preferentially exported from the nucleus immediately after synthesis and processing. J Virol. 2002;76(8):3928–35.

    PubMed Central  CAS  PubMed  Google Scholar 

  77. Zuccola HJ, Rozzelle JE, Lemon SM, Erickson BW, Hogle JM. Structural basis of the oligomerization of hepatitis delta antigen. Structure. 1998;6(7):821–30.

    CAS  PubMed  Google Scholar 

  78. Lee CZ, Lin JH, Chao M, McKnight K, Lai MM. RNA-binding activity of hepatitis delta antigen involves two arginine-rich motifs and is required for hepatitis delta virus RNA replication. J Virol. 1993;67(4):2221–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  79. Daigh LH, Griffin BL, Soroush A, Mamedov MR, Casey JL. Arginine-rich motifs are not required for hepatitis delta virus RNA binding activity of the hepatitis delta antigen. J Virol. 2013;87(15):8665–74.

    PubMed Central  CAS  PubMed  Google Scholar 

  80. Poisson F, Roingeard P, Baillou A, Dubois F, Bonelli F, Calogero RA, et al. Characterization of RNA-binding domains of hepatitis delta antigen. J Gen Virol. 1993;74(Pt 11):2473–8.

    CAS  PubMed  Google Scholar 

  81. Wang CC, Chang TC, Lin CW, Tsui HL, Chu PB, Chen BS, et al. Nucleic acid binding properties of the nucleic acid chaperone domain of hepatitis delta antigen. Nucleic Acids Res. 2003;31(22):6481–92.

    PubMed Central  CAS  PubMed  Google Scholar 

  82. Lee CH, Chang SC, Wu CH, Chang MF. A novel chromosome region maintenance 1-independent nuclear export signal of the large form of hepatitis delta antigen that is required for the viral assembly. J Biol Chem. 2001;276(11):8142–8.

    CAS  PubMed  Google Scholar 

  83. Glenn JS, Watson JA, Havel CM, White JM. Identification of a prenylation site in delta virus large antigen. Science. 1992;256(5061):1331–3.

    CAS  PubMed  Google Scholar 

  84. Otto JC, Casey PJ. The hepatitis delta virus large antigen is farnesylated both in vitro and in animal cells. J Biol Chem. 1996;271(9):4569–72.

    CAS  PubMed  Google Scholar 

  85. Chang FL, Chen PJ, Tu SJ, Wang CJ, Chen DS. The large form of hepatitis delta antigen is crucial for assembly of hepatitis delta virus. Proc Natl Acad Sci U S A. 1991;88(19):8490–4.

    PubMed Central  CAS  PubMed  Google Scholar 

  86. Chai N, Chang HE, Nicolas E, Han Z, Jarnik M, Taylor J. Properties of subviral particles of hepatitis B virus. J Virol. 2008;82(16):7812–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  87. Huang C, Chang SC, Yu IC, Tsay YG, Chang MF. Large hepatitis delta antigen is a novel clathrin adaptor-like protein. J Virol. 2007;81(11):5985–94.

    PubMed Central  CAS  PubMed  Google Scholar 

  88. Huang C, Chang SC, Yang HC, Chien CL, Chang MF. Clathrin-mediated post-Golgi membrane trafficking in the morphogenesis of hepatitis delta virus. J Virol. 2009;83(23):12314–24.

    PubMed Central  CAS  PubMed  Google Scholar 

  89. Wang YC, Huang CR, Chao M, Lo SJ. The C-terminal sequence of the large hepatitis delta antigen is variable but retains the ability to bind clathrin. Virol J. 2009;6:31.

    PubMed Central  PubMed  Google Scholar 

  90. Radjef N, Gordien E, Ivaniushina V, Gault E, Anais P, Drugan T, et al. Molecular phylogenetic analyses indicate a wide and ancient radiation of African hepatitis delta virus, suggesting a deltavirus genus of at least seven major clades. J Virol. 2004;78(5):2537–44.

    PubMed Central  CAS  PubMed  Google Scholar 

  91. Heermann KH, Gerlich WH. Surface proteins of hepatitis B viruses. In: Maclachlan A, editor. Molecular Biology of the Hepatitis B Virus. Boca Raton, Florida, USA: CRC Press; 1991. p. 109–44.

    Google Scholar 

  92. Patient R, Hourioux C, Sizaret PY, Trassard S, Sureau C, Roingeard P. Hepatitis B virus subviral envelope particle morphogenesis and intracellular trafficking. J Virol. 2007;81(8):3842–51.

    PubMed Central  CAS  PubMed  Google Scholar 

  93. Bruss V. Hepatitis B, virus morphogenesis. World J Gastroenterol. 2007;13(1):65–73.

    PubMed Central  CAS  PubMed  Google Scholar 

  94. Kian Chua P, Lin MH, Shih C. Potent inhibition of human Hepatitis B virus replication by a host factor Vps4. Virology. 2006;354(1):1–6.

    CAS  PubMed  Google Scholar 

  95. Lambert C, Doring T, Prange R. Hepatitis B virus maturation is sensitive to functional inhibition of ESCRT-III, Vps4, and gamma 2-adaptin. J Virol. 2007;81(17):9050–60.

    PubMed Central  CAS  PubMed  Google Scholar 

  96. Watanabe T, Sorensen EM, Naito A, Schott M, Kim S, Ahlquist P. Involvement of host cellular multivesicular body functions in hepatitis B virus budding. Proc Natl Acad Sci U S A. 2007;104(24):10205–10.

    PubMed Central  CAS  PubMed  Google Scholar 

  97. Barrera A, Guerra B, Lee H, Lanford RE. Analysis of host range phenotypes of primate hepadnaviruses by in vitro infections of hepatitis D virus pseudotypes. J Virol. 2004;78(10):5233–43.

    PubMed Central  CAS  PubMed  Google Scholar 

  98. Liu YT, Brazas R, Ganem D. Efficient hepatitis delta virus RNA replication in avian cells requires a permissive factor(s) from mammalian cells. J Virol. 2001;75(16):7489–93.

    PubMed Central  CAS  PubMed  Google Scholar 

  99. O’Malley B, Lazinski D. A hepatitis B surface antigen mutant that lacks the antigenic loop region can self-assemble and interact with the large hepatitis delta antigen. J Virol. 2002;76(19):10060–3.

    PubMed Central  PubMed  Google Scholar 

  100. Chen PJ, Lai WJ, Wang CJ, Chen DS. Hepatitis B surface antigen and large-form hepatitis delta antigen in HDV assembly: a further study. Prog Clin Biol Res. 1993;382:29–34.

    CAS  PubMed  Google Scholar 

  101. Freitas N, Abe K, Cunha C, Menne S, Gudima SO. Support of the infectivity of hepatitis delta virus particles by the envelope proteins of different genotypes of hepatitis B virus. J Virol. 2014;88(11):6255–67.

    PubMed Central  PubMed  Google Scholar 

  102. Blanchet M, Sureau C. Analysis of the cytosolic domains of the hepatitis B virus envelope proteins for their function in viral particle assembly and infectivity. J Virol. 2006;80(24):11935–45.

    PubMed Central  CAS  PubMed  Google Scholar 

  103. Heermann KH, Goldmann U, Schwartz W, Seyffarth T, Baumgarten H, Gerlich WH. Large surface proteins of hepatitis B virus containing the pre-s sequence. J Virol. 1984;52(2):396–402.

    PubMed Central  CAS  PubMed  Google Scholar 

  104. Le Duff Y, Blanchet M, Sureau C. The pre-S1 and antigenic loop infectivity determinants of the hepatitis B virus envelope proteins are functionally independent. J Virol. 2009;83(23):12443–51.

    PubMed Central  PubMed  Google Scholar 

  105. Sureau C. The use of hepatocytes to investigate HDV infection: the HDV/HepaRG model. Methods Mol Biol. 2010;640:463–73.

    CAS  PubMed  Google Scholar 

  106. Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife. 2012;1:e00049.

    PubMed Central  PubMed  Google Scholar 

  107. Lamas Longarela O, Schmidt TT, Schoneweis K, Romeo R, Wedemeyer H, Urban S, et al. Proteoglycans act as cellular hepatitis delta virus attachment receptors. PLoS One. 2013;8(3):e58340.

    PubMed Central  PubMed  Google Scholar 

  108. Leistner CM, Gruen-Bernhard S, Glebe D. Role of glycosaminoglycans for binding and infection of hepatitis B virus. Cell Microbiol. 2008;10(1):122–33.

    CAS  PubMed  Google Scholar 

  109. Schulze A, Gripon P, Urban S. Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans. Hepatology. 2007;46(6):1759–68.

    CAS  PubMed  Google Scholar 

  110. Sureau C, Salisse J. A conformational heparan sulfate binding site essential to infectivity overlaps with the conserved hepatitis B virus A-determinant. Hepatology. 2013;57(3):985–94.

    CAS  PubMed  Google Scholar 

  111. Abou-Jaoude G, Sureau C. Entry of hepatitis delta virus requires the conserved cysteine residues of the hepatitis B virus envelope protein antigenic loop and is blocked by inhibitors of thiol-disulfide exchange. J Virol. 2007;81(23):13057–66.

    PubMed Central  CAS  PubMed  Google Scholar 

  112. Salisse J, Sureau C. A function essential to viral entry underlies the hepatitis B virus "a" determinant. J Virol. 2009;83(18):9321–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  113. Ni Y, Lempp FA, Mehrle S, Nkongolo S, Kaufman C, Falth M, et al. Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes. Gastroenterology. 2014;146(4):1070–83.

    CAS  PubMed  Google Scholar 

  114. Blanchet M, Sureau C. Infectivity determinants of the hepatitis B virus pre-S domain are confined to the N-terminal 75 amino acid residues. J Virol. 2007;81(11):5841–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  115. Barrera A, Guerra B, Notvall L, Lanford RE. Mapping of the hepatitis B virus pre-S1 domain involved in receptor recognition. J Virol. 2005;79(15):9786–98.

    PubMed Central  CAS  PubMed  Google Scholar 

  116. Engelke M, Mills K, Seitz S, Simon P, Gripon P, Schnolzer M, et al. Characterization of a hepatitis B and hepatitis delta virus receptor binding site. Hepatology. 2006;43(4):750–60.

    CAS  PubMed  Google Scholar 

  117. Glebe D, Urban S, Knoop EV, Cag N, Krass P, Grun S, et al. Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes. Gastroenterology. 2005;129(1):234–45.

    CAS  PubMed  Google Scholar 

  118. Gripon P, Cannie I, Urban S. Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein. J Virol. 2005;79(3):1613–22.

    PubMed Central  CAS  PubMed  Google Scholar 

  119. Hong HJ, Ryu CJ, Hur H, Kim S, Oh HK, Oh MS, et al. In vivo neutralization of hepatitis B virus infection by an anti-preS1 humanized antibody in chimpanzees. Virology. 2004;318(1):134–41.

    CAS  PubMed  Google Scholar 

  120. Le Seyec J, Chouteau P, Cannie I, Guguen-Guillouzo C, Gripon P. Infection process of the hepatitis B virus depends on the presence of a defined sequence in the pre-S1 domain. J Virol. 1999;73(3):2052–7.

    PubMed Central  PubMed  Google Scholar 

  121. Maeng CY, Ryu CJ, Gripon P, Guguen-Guillouzo C, Hong HJ. Fine mapping of virus-neutralizing epitopes on hepatitis B virus PreS1. Virology. 2000;270(1):9–16.

    CAS  PubMed  Google Scholar 

  122. Petersen J, Dandri M, Mier W, Lutgehetmann M, Volz T, von Weizsacker F, et al. Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein. Nat Biotechnol. 2008;26(3):335–41.

    CAS  PubMed  Google Scholar 

  123. Schulze A, Schieck A, Ni Y, Mier W, Urban S. Fine mapping of pre-S sequence requirements for hepatitis B virus large envelope protein-mediated receptor interaction. J Virol. 2010;84(4):1989–2000.

    PubMed Central  CAS  PubMed  Google Scholar 

  124. Kann M, Schmitz A, Rabe B. Intracellular transport of hepatitis B virus. World J Gastroenterol. 2007;13(1):39–47.

    PubMed Central  CAS  PubMed  Google Scholar 

  125. Bremer CM, Bung C, Kott N, Hardt M, Glebe D. Hepatitis B virus infection is dependent on cholesterol in the viral envelope. Cell Microbiol. 2009;11(2):249–60.

    CAS  PubMed  Google Scholar 

  126. Cooper A, Shaul Y. Clathrin-mediated endocytosis and lysosomal cleavage of hepatitis B virus capsid-like core particles. J Biol Chem. 2006;281(24):16563–9.

    CAS  PubMed  Google Scholar 

  127. Huang HC, Chen CC, Chang WC, Tao MH, Huang C. Entry of hepatitis B virus into immortalized human primary hepatocytes by clathrin-dependent endocytosis. J Virol. 2012;86(17):9443–53.

    PubMed Central  CAS  PubMed  Google Scholar 

  128. Macovei A, Radulescu C, Lazar C, Petrescu S, Durantel D, Dwek RA, et al. Hepatitis B virus requires intact caveolin-1 function for productive infection in HepaRG cells. J Virol. 2010;84(1):243–53.

    PubMed Central  CAS  PubMed  Google Scholar 

  129. Chen PJ, Chen DS, Chen CR, Chen YY, Chen HM, Lai MY, et al. Delta infection in asymptomatic carriers of hepatitis B surface antigen: low prevalence of delta activity and effective suppression of hepatitis B virus replication. Hepatology. 1988;8(5):1121–4.

    CAS  PubMed  Google Scholar 

  130. Wu JC, Chen PJ, Kuo MY, Lee SD, Chen DS, Ting LP. Production of hepatitis delta virus and suppression of helper hepatitis B virus in a human hepatoma cell line. J Virol. 1991;65(3):1099–104.

    PubMed Central  CAS  PubMed  Google Scholar 

  131. Williams V, Brichler S, Radjef N, Lebon P, Goffard A, Hober D, et al. Hepatitis delta virus proteins repress hepatitis B virus enhancers and activate the alpha/beta interferon-inducible MxA gene. J Gen Virol. 2009;90(Pt 11):2759–67.

    CAS  PubMed  Google Scholar 

  132. Giersch K, Helbig M, Volz T, Allweiss L, Mancke LV, Lohse AW, et al. Persistent hepatitis D virus mono-infection in humanized mice is efficiently converted by hepatitis B virus to a productive co-infection. J Hepatol. 2014;60(3):538–44. PubMed Epub 2013/11/28. eng.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Virologie Moléculaire, Institut National de la Transfusion Sanguine, 6 rue Alexandre Cabanel, 75749, Paris, France

    Camille Sureau

Authors
  1. Camille Sureau
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Camille Sureau .

Editor information

Editors and Affiliations

  1. Chang Gung University, Chang Gung Memorial Hospital, Taipei, Taiwan

    Yun-Fan Liaw

  2. INSERM Unit 1052, Hospices Civils de Lyon, Lyon University, Lyon, France

    Fabien Zoulim

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Sureau, C. (2016). Hepatitis Delta Virus: Virology and Replication. In: Liaw, YF., Zoulim, F. (eds) Hepatitis B Virus in Human Diseases. Molecular and Translational Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-22330-8_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-22330-8_7

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-22329-2

  • Online ISBN: 978-3-319-22330-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation