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Semin Liver Dis 2013; 33(02): 103-112
DOI: 10.1055/s-0033-1345717
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Molecular Virology of Hepatitis B Virus

Dieter Glebe
1   Institute of Medical Virology, National Reference Centre for Hepatitis B and D Viruses, Justus-Liebig University of Giessen, Giessen, Germany
,
Corinna M. Bremer
1   Institute of Medical Virology, National Reference Centre for Hepatitis B and D Viruses, Justus-Liebig University of Giessen, Giessen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
08 June 2013 (online)

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Abstract

Hepatitis B virus (HBV) is one of the smallest enveloped DNA viruses and the prototype member of the family of Hepadnaviridae that causes acute and chronic infections of mammals (including human) and birds. HBV has evolved an extreme adaptation and dependency to differentiated hepatocytes of its host. Despite its very limited coding capacity with only four open-reading frames, HBV is able to evade the immune system of the host and persist lifelong within infected hepatocytes. During active replication, HBV produces enormous viral loads in the blood and a massive surplus of subviral surface antigen particles in the serum of infected patients without killing their hepatocytes. Together with the use of a reverse transcriptase during replication, it provides an enormous genetic flexibility for selection of viral mutants upon selective pressure, for example, by the immune system or antiviral therapy. In addition, viral wild-type and mutated genomes are stably archived in the nucleus of the infected hepatocyte in an episomal DNA form that provides independence from cellular replication or integration within the host genome. We are just beginning to understand the delicate molecular and cellular interactions during the HBV replicative cycle within infected hepatocytes, so further studies are urgently needed to provide a better basis for further diagnostic and therapeutic options.

Keywords

hepatitis B virus - receptor - viral entry - sodium taurocholate cotransporting polypeptide - replication - cccDNA
 

  • References

  • 1 Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 2012; 30 (12) 2212-2219
    CrossrefPubMedGoogle Scholar
  • 2 International Committee on Taxonomy of Viruses (ICTV). Virus Taxonomy. 2012. Available at: http://www.ictvonline.org/index.asp . Accessed February 12, 2013
    PubMedGoogle Scholar
  • 3 Landers TA, Greenberg HB, Robinson WS. Structure of hepatitis B Dane particle DNA and nature of the endogenous DNA polymerase reaction. J Virol 1977; 23 (2) 368-376
    PubMedGoogle Scholar
  • 4 Beck J, Nassal M. Hepatitis B virus replication. World J Gastroenterol 2007; 13 (1) 48-64
    CrossrefPubMedGoogle Scholar
  • 5 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
    PubMedGoogle Scholar
  • 6 Glebe D, Urban S. Viral and cellular determinants involved in hepadnaviral entry. World J Gastroenterol 2007; 13 (1) 22-38
    PubMedGoogle Scholar
  • 7 Garcia PD, Ou JH, Rutter WJ, Walter P. 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 1988; 106 (4) 1093-1104
    CrossrefPubMedGoogle Scholar
  • 8 Magnius LO, Espmark A. A new antigen complex co-occurring with Australia antigen. Acta Pathologica et Microbiologica Scandinavica Section B. Microbiol Immunol 1972; 80 (2) 335-337
    PubMedGoogle Scholar
  • 9 Kew MC. Hepatitis B virus x protein in the pathogenesis of hepatitis B virus-induced hepatocellular carcinoma. J Gastroenterol Hepatol 2011; 26 (Suppl. 01) 144-152
    CrossrefPubMedGoogle Scholar
  • 10 Lucifora J, Arzberger S, Durantel D , et al. Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection. J Hepatol 2011; 55 (5) 996-1003
    CrossrefPubMedGoogle Scholar
  • 11 Seitz S, Urban S, Antoni C, Böttcher B. Cryo-electron microscopy of hepatitis B virions reveals variability in envelope capsid interactions. EMBO J 2007; 26 (18) 4160-4167
    CrossrefPubMedGoogle Scholar
  • 12 Dryden KA, Wieland SF, Whitten-Bauer C, Gerin JL, Chisari FV, Yeager M. Native hepatitis B virions and capsids visualized by electron cryomicroscopy. Mol Cell 2006; 22 (6) 843-850
    CrossrefPubMedGoogle Scholar
  • 13 Kann M, Gerlich WH. Effect of core protein phosphorylation by protein kinase C on encapsidation of RNA within core particles of hepatitis B virus. J Virol 1994; 68 (12) 7993-8000
    PubMedGoogle Scholar
  • 14 Wittkop L, Schwarz A, Cassany A , et al. Inhibition of protein kinase C phosphorylation of hepatitis B virus capsids inhibits virion formation and causes intracellular capsid accumulation. Cell Microbiol 2010; 12 (7) 962-975
    CrossrefPubMedGoogle Scholar
  • 15 Kau JH, Ting LP. Phosphorylation of the core protein of hepatitis B virus by a 46-kilodalton serine kinase. J Virol 1998; 72 (5) 3796-3803
    PubMedGoogle Scholar
  • 16 Raney AK, Easton AJ, Milich DR, McLachlan A. Promoter-specific transactivation of hepatitis B virus transcription by a glutamine- and proline-rich domain of hepatocyte nuclear factor 1. J Virol 1991; 65 (11) 5774-5781
    PubMedGoogle Scholar
  • 17 Cattaneo R, Will H, Hernandez N, Schaller H. Signals regulating hepatitis B surface antigen transcription. Nature 1983; 305 (5932) 336-338
    CrossrefPubMedGoogle Scholar
  • 18 Berting A, Hahnen J, Kröger M, Gerlich WH. Computer-aided studies on the spatial structure of the small hepatitis B surface protein. Intervirology 1995; 38 (1-2) 8-15
    PubMedGoogle Scholar
  • 19 Eble BE, Lingappa VR, Ganem D. The N-terminal (pre-S2) domain of a hepatitis B virus surface glycoprotein is translocated across membranes by downstream signal sequences. J Virol 1990; 64 (3) 1414-1419
    PubMedGoogle Scholar
  • 20 Schmitt S, Glebe D, Alving K , et al. Analysis of the pre-S2 N- and O-linked glycans of the M surface protein from human hepatitis B virus. J Biol Chem 1999; 274 (17) 11945-11957
    CrossrefPubMedGoogle Scholar
  • 21 Schmitt S, Glebe D, Tolle TK , et al. Structure of pre-S2 N- and O-linked glycans in surface proteins from different genotypes of hepatitis B virus. J Gen Virol 2004; 85 (Pt 7) 2045-2053
    CrossrefPubMedGoogle Scholar
  • 22 Löffler-Mary H, Dumortier J, Klentsch-Zimmer C, Prange R. Hepatitis B virus assembly is sensitive to changes in the cytosolic S loop of the envelope proteins. Virology 2000; 270 (2) 358-367
    CrossrefPubMedGoogle Scholar
  • 23 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) 2052-2057
    PubMedGoogle Scholar
  • 24 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) 1759-1768
    CrossrefPubMedGoogle Scholar
  • 25 Glebe D, Urban S, Knoop EV , et al. Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes. Gastroenterology 2005; 129 (1) 234-245
    CrossrefPubMedGoogle Scholar
  • 26 Glebe D, Aliakbari M, Krass P, Knoop EV, Valerius KP, Gerlich WH. Pre-S1 antigen-dependent infection of Tupaia hepatocyte cultures with human hepatitis B virus. J Virol 2003; 77 (17) 9511-9521
    CrossrefPubMedGoogle Scholar
  • 27 Ostapchuk P, Hearing P, Ganem D. A dramatic shift in the transmembrane topology of a viral envelope glycoprotein accompanies hepatitis B viral morphogenesis. EMBO J 1994; 13 (5) 1048-1057
    PubMedGoogle Scholar
  • 28 Bruss V, Lu X, Thomssen R, Gerlich WH. Post-translational alterations in transmembrane topology of the hepatitis B virus large envelope protein. EMBO J 1994; 13 (10) 2273-2279
    PubMedGoogle Scholar
  • 29 Prange R, Streeck RE. Novel transmembrane topology of the hepatitis B virus envelope proteins. EMBO J 1995; 14 (2) 247-256
    PubMedGoogle Scholar
  • 30 Lambert C, Prange R. Dual topology of the hepatitis B virus large envelope protein: determinants influencing post-translational pre-S translocation. J Biol Chem 2001; 276 (25) 22265-22272
    CrossrefPubMedGoogle Scholar
  • 31 Lambert C, Mann S, Prange R. Assessment of determinants affecting the dual topology of hepadnaviral large envelope proteins. J Gen Virol 2004; 85 (Pt 5) 1221-1225
    CrossrefPubMedGoogle Scholar
  • 32 Leistner CM, Gruen-Bernhard S, Glebe D. Role of glycosaminoglycans for binding and infection of hepatitis B virus. Cell Microbiol 2008; 10 (1) 122-133
    PubMedGoogle Scholar
  • 33 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) 985-994
    CrossrefPubMedGoogle Scholar
  • 34 Glebe D. Attachment sites and neutralising epitopes of hepatitis B virus. Minerva Gastroenterol Dietol 2006; 52 (1) 3-21
    PubMedGoogle Scholar
  • 35 Yan H, Zhong G, Xu G , et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife 2012; 1: 49
    CrossrefPubMedGoogle Scholar
  • 36 Chouteau P, Le Seyec J, Cannie I, Nassal M, Guguen-Guillouzo C, Gripon P. A short N-proximal region in the large envelope protein harbors a determinant that contributes to the species specificity of human hepatitis B virus. J Virol 2001; 75 (23) 11565-11572
    CrossrefPubMedGoogle Scholar
  • 37 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) 9786-9798
    CrossrefPubMedGoogle Scholar
  • 38 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) 5841-5849
    CrossrefPubMedGoogle Scholar
  • 39 Bruss V, Hagelstein J, Gerhardt E, Galle PR. Myristylation of the large surface protein is required for hepatitis B virus in vitro infectivity. Virology 1996; 218 (2) 396-399
    CrossrefPubMedGoogle Scholar
  • 40 Gripon P, Le Seyec J, Rumin S, Guguen-Guillouzo C. Myristylation of the hepatitis B virus large surface protein is essential for viral infectivity. Virology 1995; 213 (2) 292-299
    CrossrefPubMedGoogle Scholar
  • 41 Gripon P, Rumin S, Urban S , et al. Infection of a human hepatoma cell line by hepatitis B virus. Proc Natl Acad Sci U S A 2002; 99 (24) 15655-15660
    CrossrefPubMedGoogle Scholar
  • 42 Petersen J, Dandri M, Mier W , et al. Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein. Nat Biotechnol 2008; 26 (3) 335-341
    CrossrefPubMedGoogle Scholar
  • 43 Volz T, Allweiss L , M Barek MB, et al. The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus. J Hepatol 2012;
    PubMedGoogle Scholar
  • 44 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) 1613-1622
    CrossrefPubMedGoogle Scholar
  • 45 Urban S, Gripon P. Inhibition of duck hepatitis B virus infection by a myristoylated pre-S peptide of the large viral surface protein. J Virol 2002; 76 (4) 1986-1990
    CrossrefPubMedGoogle Scholar
  • 46 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
    CrossrefPubMedGoogle Scholar
  • 47 Engelke M, Mills K, Seitz S , et al. Characterization of a hepatitis B and hepatitis delta virus receptor binding site. Hepatology 2006; 43 (4) 750-760
    CrossrefPubMedGoogle Scholar
  • 48 Niedre-Otomere B, Bogdanova A, Skrastina D , et al. Recombinant Semliki Forest virus vectors encoding hepatitis B virus small surface and pre-S1 antigens induce broadly reactive neutralizing antibodies. J Viral Hepat 2012; 19 (9) 664-673
    CrossrefPubMedGoogle Scholar
  • 49 Bremer CM, Sominskaya I, Skrastina D , et al. N-terminal myristoylation-dependent masking of neutralizing epitopes in the preS1 attachment site of hepatitis B virus. J Hepatol 2011; 55 (1) 29-37
    CrossrefPubMedGoogle Scholar
  • 50 Salisse J, Sureau C. A function essential to viral entry underlies the hepatitis B virus “a” determinant. J Virol 2009; 83 (18) 9321-9328
    CrossrefPubMedGoogle Scholar
  • 51 Lepère-Douard C, Trotard M, Le Seyec J, Gripon P. The first transmembrane domain of the hepatitis B virus large envelope protein is crucial for infectivity. J Virol 2009; 83 (22) 11819-11829
    CrossrefPubMedGoogle Scholar
  • 52 Abou-Jaoudé 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) 13057-13066
    CrossrefPubMedGoogle Scholar
  • 53 Berting A, Fischer C, Schaefer S, Garten W, Klenk HD, Gerlich WH. Hemifusion activity of a chimeric influenza virus hemagglutinin with a putative fusion peptide from hepatitis B virus. Virus Res 2000; 68 (1) 35-49
    CrossrefPubMedGoogle Scholar
  • 54 Fernholz D, Galle PR, Stemler M, Brunetto M, Bonino F, Will H. Infectious hepatitis B virus variant defective in pre-S2 protein expression in a chronic carrier. Virology 1993; 194 (1) 137-148
    CrossrefPubMedGoogle Scholar
  • 55 Sureau C, Guerra B, Lee H. The middle hepatitis B virus envelope protein is not necessary for infectivity of hepatitis delta virus. J Virol 1994; 68 (6) 4063-4066
    PubMedGoogle Scholar
  • 56 Ni Y, Sonnabend J, Seitz S, Urban S. The pre-s2 domain of the hepatitis B virus is dispensable for infectivity but serves a spacer function for L-protein-connected virus assembly. J Virol 2010; 84 (8) 3879-3888
    CrossrefPubMedGoogle Scholar
  • 57 Stoeckl L, Funk A, Kopitzki A , et al. Identification of a structural motif crucial for infectivity of hepatitis B viruses. Proc Natl Acad Sci U S A 2006; 103 (17) 6730-6734
    CrossrefPubMedGoogle Scholar
  • 58 Wang HC, Huang W, Lai MD, Su IJ. Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesis. Cancer Sci 2006; 97 (8) 683-688
    CrossrefPubMedGoogle Scholar
  • 59 Mercer J, Schelhaas M, Helenius A. Virus entry by endocytosis. Annu Rev Biochem 2010; 79: 803-833
    CrossrefPubMedGoogle Scholar
  • 60 Gavilanes F, Gonzalez-Ros JM, Peterson DL. Structure of hepatitis B surface antigen. Characterization of the lipid components and their association with the viral proteins. J Biol Chem 1982; 257 (13) 7770-7777
    PubMedGoogle Scholar
  • 61 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) 249-260
    CrossrefPubMedGoogle Scholar
  • 62 Graham DR, Chertova E, Hilburn JM, Arthur LO, Hildreth JE. Cholesterol depletion of human immunodeficiency virus type 1 and simian immunodeficiency virus with beta-cyclodextrin inactivates and permeabilizes the virions: evidence for virion-associated lipid rafts. J Virol 2003; 77 (15) 8237-8248
    CrossrefPubMedGoogle Scholar
  • 63 Rabe B, Glebe D, Kann M. Lipid-mediated introduction of hepatitis B virus capsids into nonsusceptible cells allows highly efficient replication and facilitates the study of early infection events. J Virol 2006; 80 (11) 5465-5473
    CrossrefPubMedGoogle Scholar
  • 64 Schmitz A, Schwarz A, Foss M , et al. Nucleoporin 153 arrests the nuclear import of hepatitis B virus capsids in the nuclear basket. PLoS Pathog 2010; 6 (1) e1000741
    CrossrefPubMedGoogle Scholar
  • 65 Rabe B, Delaleau M, Bischof A , et al. Nuclear entry of hepatitis B virus capsids involves disintegration to protein dimers followed by nuclear reassociation to capsids. PLoS Pathog 2009; 5 (8) e1000563
    CrossrefPubMedGoogle Scholar
  • 66 Köck J, Rösler C, Zhang JJ, Blum HE, Nassal M, Thoma C. Generation of covalently closed circular DNA of hepatitis B viruses via intracellular recycling is regulated in a virus specific manner. PLoS Pathog 2010; 6 (9) e1001082
    CrossrefPubMedGoogle Scholar
  • 67 Levrero M, Pollicino T, Petersen J, Belloni L, Raimondo G, Dandri M. Control of cccDNA function in hepatitis B virus infection. J Hepatol 2009; 51 (3) 581-592
    CrossrefPubMedGoogle Scholar
  • 68 Vartanian JP, Henry M, Marchio A , et al. Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis. PLoS Pathog 2010; 6 (5) e1000928
    CrossrefPubMedGoogle Scholar
  • 69 Grimm D, Heeg M, Thimme R. Hepatitis B virus: from immunobiology to immunotherapy. Clin Sci (Lond) 2013; 124 (2) 77-85
    CrossrefPubMedGoogle Scholar
  • 70 Gerelsaikhan T, Tavis JE, Bruss V. Hepatitis B virus nucleocapsid envelopment does not occur without genomic DNA synthesis. J Virol 1996; 70 (7) 4269-4274
    PubMedGoogle Scholar
  • 71 Bruss V. A short linear sequence in the pre-S domain of the large hepatitis B virus envelope protein required for virion formation. J Virol 1997; 71 (12) 9350-9357
    PubMedGoogle Scholar
  • 72 Tan WS, Dyson MR, Murray K. Two distinct segments of the hepatitis B virus surface antigen contribute synergistically to its association with the viral core particles. J Mol Biol 1999; 286 (3) 797-808
    CrossrefPubMedGoogle Scholar
  • 73 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) 11935-11945
    CrossrefPubMedGoogle Scholar
  • 74 Poisson F, Severac A, Hourioux C, Goudeau A, Roingeard P. Both pre-S1 and S domains of hepatitis B virus envelope proteins interact with the core particle. Virology 1997; 228 (1) 115-120
    CrossrefPubMedGoogle Scholar
  • 75 Lambert C, Döring 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) 9050-9060
    CrossrefPubMedGoogle Scholar
  • 76 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) 10205-10210
    CrossrefPubMedGoogle Scholar
  • 77 Morita E. Differential requirements of mammalian ESCRTs in multivesicular body formation, virus budding and cell division. FEBS J 2012; 279 (8) 1399-1406
    CrossrefPubMedGoogle Scholar
  • 78 Guizetti J, Schermelleh L, Mäntler J , et al. Cortical constriction during abscission involves helices of ESCRT-III-dependent filaments. Science 2011; 331 (6024) 1616-1620
    CrossrefPubMedGoogle Scholar
  • 79 Guizetti J, Gerlich DW. ESCRT-III polymers in membrane neck constriction. Trends Cell Biol 2012; 22 (3) 133-140
    CrossrefPubMedGoogle Scholar
  • 80 Hurley JH, Hanson PI. Membrane budding and scission by the ESCRT machinery: it's all in the neck. Nat Rev Mol Cell Biol 2010; 11 (8) 556-566
    CrossrefPubMedGoogle Scholar
  • 81 Weiss ER, Göttlinger H. The role of cellular factors in promoting HIV budding. J Mol Biol 2011; 410 (4) 525-533
    CrossrefPubMedGoogle Scholar
  • 82 Rost M, Mann S, Lambert C, Döring T, Thomé N, Prange R. Gamma-adaptin, a novel ubiquitin-interacting adaptor, and Nedd4 ubiquitin ligase control hepatitis B virus maturation. J Biol Chem 2006; 281 (39) 29297-29308
    CrossrefPubMedGoogle Scholar
  • 83 Pairan A, Bruss V. Functional surfaces of the hepatitis B virus capsid. J Virol 2009; 83 (22) 11616-11623
    CrossrefPubMedGoogle Scholar
  • 84 Sun D, Nassal M. Stable HepG2- and Huh7-based human hepatoma cell lines for efficient regulated expression of infectious hepatitis B virus. J Hepatol 2006; 45 (5) 636-645
    CrossrefPubMedGoogle Scholar
  • 85 Bardens A, Döring T, Stieler J, Prange R. Alix regulates egress of hepatitis B virus naked capsid particles in an ESCRT-independent manner. Cell Microbiol 2011; 13 (4) 602-619
    CrossrefPubMedGoogle Scholar
  • 86 Possehl C, Repp R, Heermann KH, Korec E, Uy A, Gerlich WH. Absence of free core antigen in anti-HBc negative viremic hepatitis B carriers. Arch Virol Suppl 1992; 4: 39-41
    PubMedGoogle Scholar
  • 87 Eble BE, MacRae DR, Lingappa VR, Ganem D. Multiple topogenic sequences determine the transmembrane orientation of the hepatitis B surface antigen. Mol Cell Biol 1987; 7 (10) 3591-3601
    PubMedGoogle Scholar
  • 88 Patzer EJ, Nakamura GR, Simonsen CC, Levinson AD, Brands R. Intracellular assembly and packaging of hepatitis B surface antigen particles occur in the endoplasmic reticulum. J Virol 1986; 58 (3) 884-892
    PubMedGoogle Scholar
  • 89 Bruss V, Ganem D. Mutational analysis of hepatitis B surface antigen particle assembly and secretion. J Virol 1991; 65 (7) 3813-3820
    PubMedGoogle Scholar
  • 90 Huovila AP, Eder AM, Fuller SD. Hepatitis B surface antigen assembles in a post-ER, pre-Golgi compartment. J Cell Biol 1992; 118 (6) 1305-1320
    CrossrefPubMedGoogle Scholar
  • 91 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) 3842-3851
    CrossrefPubMedGoogle Scholar
  • 92 Patient R, Hourioux C, Roingeard P. Morphogenesis of hepatitis B virus and its subviral envelope particles. Cell Microbiol 2009; 11 (11) 1561-1570
    CrossrefPubMedGoogle Scholar