Entry of hepatitis B and hepatitis D virus into hepatocytes: Basic insights and clinical implications

Journal of Hepatology

Volumn 64, Issue 1, 2016, Pages S32-S40

  Li, Wenhui ^a   Urban, Stephan ^b,c  

^a NATIONAL INSTITUTE OF BIOLOGICAL SCIENCES   (China)

^b UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^c German Centre for Infectious Diseases (DZIF)   (Germany)

Author keywords

Hepatitis B virus entry; Hepatitis B virus receptor; Myrcludex B; NTCP; SLC10A1

Indexed keywords

ALISPORIVIR; ANTIVIRUS AGENT; BILE ACID CONJUGATE; CIRCULAR DNA; COVALENTLY CLOSED CIRCULAR DNA; CYCLOSPORIN A; ENFUVIRTIDE; EZETIMIBE; GLYCOCHOLIC ACID; HOST FACTOR; LIPOPEPTIDE; MARAVIROC; MONOCLONAL ANTIBODY; MYRCLUDEX B; NEUTRALIZING ANTIBODY; SODIUM BILE ACID COTRANSPORTER; TAUROCHOLIC ACID; UNCLASSIFIED DRUG; VIRUS ENVELOPE PROTEIN; VIRUS RECEPTOR;

ANTIVIRAL ACTIVITY; CLINICAL OUTCOME; CLINICAL RESEARCH; DRUG EFFICACY; DRUG SAFETY; HEP-G2 CELL LINE; HEPATITIS B; HEPATITIS B VIRUS; HEPATITIS DELTA VIRUS; HIGH THROUGHPUT SCREENING; LIVER CELL; PHASE 1 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW; SCREENING; VIRUS CELL INTERACTION; VIRUS ENTRY; VIRUS PATHOGENESIS; VIRUS REPLICATION; ANIMAL; CELL LINE; DELTA AGENT HEPATITIS; HUMAN; ISOLATION AND PURIFICATION; PATHOGENICITY; PATHOLOGY; VIROLOGY;

ANIMALS; CELL LINE; HEPATITIS B; HEPATITIS B VIRUS; HEPATITIS D; HEPATITIS DELTA VIRUS; HEPATOCYTES; HUMANS; VIRUS INTERNALIZATION;

EID: 85010880304     PISSN: 01688278     EISSN: 16000641     Source Type: Journal    
DOI: 10.1016/j.jhep.2016.02.011     Document Type: Review

References (89)

1. [1] Ganem, D., Prince, A.M., Hepatitis B virus infection–natural history and clinical consequences. N Engl J Med 350 (2004), 1118–1129.
2. [2] Seeger, C., Mason, W.S., Molecular biology of hepatitis B virus infection. Virology 479–480 (2015), 672–686.
3. [3] Suk-Fong Lok, A., Hepatitis B: 50 years after the discovery of Australia antigen. J Viral Hepat 23 (2016), 5–14.
4. [4] Gripon, P., Diot, C., Theze, N., Fourel, I., Loreal, O., Brechot, C., et al. Hepatitis B virus infection of adult human hepatocytes cultured in the presence of dimethyl sulfoxide. J Virol 62 (1988), 4136–4143.
5. [5] Gripon, P., Diot, C., Corlu, A., Guguen-Guillouzo, C., Regulation by dimethylsulfoxide, insulin, and corticosteroids of hepatitis B virus replication in a transfected human hepatoma cell line. J Med Virol 28 (1989), 193–199.
6. [6] Glebe, D., Aliakbari, M., Krass, P., Knoop, E.V., Valerius, K.P., Gerlich, W.H., Pre-s1 antigen-dependent infection of Tupaia hepatocyte cultures with human hepatitis B virus. J Virol 77 (2003), 9511–9521.
7. [7] Kock, J., Baumert, T.F., Delaney, W.E. 4th, Blum, H.E., von Weizsacker, F., Inhibitory effect of adefovir and lamivudine on the initiation of hepatitis B virus infection in primary tupaia hepatocytes. Hepatology 38 (2003), 1410–1418.
8. [8] Walter, E., Keist, R., Niederost, B., Pult, I., Blum, H.E., Hepatitis B virus infection of tupaia hepatocytes in vitro and in vivo. Hepatology 24 (1996), 1–5.
9. [9] Gripon, P., Rumin, S., Urban, S., Le Seyec, J., Glaise, D., Cannie, I., et al. Infection of a human hepatoma cell line by hepatitis B virus. Proc Natl Acad Sci U S A 99 (2002), 15655–15660.
10. [10] Glebe, D., Urban, S., Viral and cellular determinants involved in hepadnaviral entry. World J Gastroenterol 13 (2007), 22–38.
11. [11] Fernholz, D., Galle, P.R., Stemler, M., Brunetto, M., Bonino, F., Will, H., Infectious hepatitis B virus variant defective in pre-S2 protein expression in a chronic carrier. Virology 194 (1993), 137–148.
12. [12] 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 84 (2010), 3879–3888.
13. [13] Sureau, C., Salisse, J., A conformational heparan sulfate binding site essential to infectivity overlaps with the conserved hepatitis B virus a-determinant. Hepatology 57 (2013), 985–994.
14. [14] 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 73 (1999), 2052–2057.
15. [15] 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 81 (2007), 5841–5849.
16. [16] Bruss, V., Hagelstein, J., Gerhardt, E., Galle, P.R., Myristylation of the large surface protein is required for hepatitis B virus in vitro infectivity. Virology 218 (1996), 396–399.
17. [17] 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 213 (1995), 292–299.
18. [18] 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 84 (2010), 1989–2000.
19. [19] 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 43 (2006), 750–760.
20. [20] Glebe, D., Urban, S., Knoop, E.V., 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 129 (2005), 234–245.
21. [21] 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 79 (2005), 1613–1622.
22. [22] 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 26 (2008), 335–341.
23. [23] 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, 1, 2012, e00049.
24. [24] Drexler, J.F., Geipel, A., Konig, A., Corman, V.M., van Riel, D., Leijten, L.M., et al. Bats carry pathogenic hepadnaviruses antigenically related to hepatitis B virus and capable of infecting human hepatocytes. Proc Natl Acad Sci U S A 110 (2013), 16151–16156.
25. [25] Zhong, G., Yan, H., Wang, H., He, W., Jing, Z., Qi, Y., et al. Sodium taurocholate cotransporting polypeptide mediates woolly monkey hepatitis B virus infection of Tupaia hepatocytes. J Virol 87 (2013), 7176–7184.
26. [26] Ni, Y., Lempp, F.A., 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 146 (2014), 1070–1083.
27. [27] Li, W., The hepatitis B virus receptor. Annu Rev Cell Dev Biol 31 (2015), 125–147.
28. [28] Anwer, M.S., Stieger, B., Sodium-dependent bile salt transporters of the SLC10A transporter family: more than solute transporters. Pflugers Arch 466 (2014), 77–89.
29. [29] Slijepcevic, D., Kaufman, C., Wichers, C.G., Gilglioni, E.H., Lempp, F.A., Duijst, S., et al. Impaired uptake of conjugated bile acids and Hepatitis B Virus preS1-binding in Na -taurocholate cotransporting polypeptide knockout mice. Hepatology 62 (2015), 207–219.
30. [30] Vaz, F.M., Paulusma, C.C., Huidekoper, H., de Ru, M., Lim, C., Koster, J., et al. Sodium taurocholate cotransporting polypeptide (SLC10A1) deficiency: Conjugated hypercholanemia without a clear clinical phenotype. Hepatology 61 (2015), 260–267.
31. [31] Stieger, B., The role of the sodium-taurocholate cotransporting polypeptide (NTCP) and of the bile salt export pump (BSEP) in physiology and pathophysiology of bile formation. Handb Exp Pharmacol, 2011, 205–259.
32. [32] Schieck, A., Schulze, A., Gahler, C., Muller, T., Haberkorn, U., Alexandrov, A., et al. Hepatitis B virus hepatotropism is mediated by specific receptor recognition in the liver and not restricted to susceptible hosts. Hepatology 58 (2013), 43–53.
33. [33] Stieger, B., Hagenbuch, B., Landmann, L., Hochli, M., Schroeder, A., Meier, P.J., In situ localization of the hepatocytic Na+/Taurocholate cotransporting polypeptide in rat liver. Gastroenterology 107 (1994), 1781–1787.
34. [34] Meier, A., Mehrle, S., Weiss, T.S., Mier, W., Urban, S., Myristoylated PreS1-domain of the hepatitis B virus L-protein mediates specific binding to differentiated hepatocytes. Hepatology 58 (2013), 31–42.
35. [35] Schulze, A., Mills, K., Weiss, T.S., Urban, S., Hepatocyte polarization is essential for the productive entry of the hepatitis B virus. Hepatology 55 (2012), 373–383.
36. [36] Kullak-Ublick, G.A., Glasa, J., Boker, C., Oswald, M., Grutzner, U., Hagenbuch, B., et al. Chlorambucil-taurocholate is transported by bile acid carriers expressed in human hepatocellular carcinomas. Gastroenterology 113 (1997), 1295–1305.
37. [37] Liang, D., Hagenbuch, B., Stieger, B., Meier, P.J., Parallel decrease of Na(+)-taurocholate cotransport and its encoding mRNA in primary cultures of rat hepatocytes. Hepatology 18 (1993), 1162–1166.
38. [38] Rippin, S.J., Hagenbuch, B., Meier, P.J., Stieger, B., Cholestatic expression pattern of sinusoidal and canalicular organic anion transport systems in primary cultured rat hepatocytes. Hepatology 33 (2001), 776–782.
39. [39] Peng, L., Zhao, Q., Li, Q., Li, M., Li, C., Xu, T., et al. The p.Ser267Phe variant in SLC10A1 is associated with resistance to chronic hepatitis B. Hepatology 61 (2015), 1251–1260.
40. [40] Pan, W., Song, I.S., Shin, H.J., Kim, M.H., Choi, Y.L., Lim, S.J., et al. Genetic polymorphisms in Na+-taurocholate co-transporting polypeptide (NTCP) and ileal apical sodium-dependent bile acid transporter (ASBT) and ethnic comparisons of functional variants of NTCP among Asian populations. Xenobiotica 41 (2011), 501–510.
41. [41] Yan, H., Peng, B., Liu, Y., Xu, G., He, W., Ren, B., et al. Viral entry of hepatitis B and D viruses and bile salts transportation share common molecular determinants on sodium taurocholate cotransporting polypeptide. J Virol 88 (2014), 3273–3284.
42. [42] Hu, H.H., Liu, J., Lin, Y.L., Luo, W.S., Chu, Y.J., Chang, C.L., et al. The rs2296651 (S267F) variant on NTCP (SLC10A1) is inversely associated with chronic hepatitis B and progression to cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B. Gut, 2015, 10.1136/gutjnl-2015-310686.
43. [43] Lucifora, J., Vincent, I.E., Berthillon, P., Dupinay, T., Michelet, M., Protzer, U., et al. Hepatitis B virus replication in primary macaque hepatocytes: crossing the species barrier toward a new small primate model. Hepatology 51 (2010), 1954–1960.
44. [44] Guidotti, L.G., Matzke, B., Schaller, H., Chisari, F.V., High-level hepatitis B virus replication in transgenic mice. J Virol 69 (1995), 6158–6169.
45. [45] Kuiken, T., Holmes, E.C., McCauley, J., Rimmelzwaan, G.F., Williams, C.S., Grenfell, B.T., Host species barriers to influenza virus infections. Science 312 (2006), 394–397.
46. [46] Lu, G., Wang, Q., Gao, G.F., Bat-to-human: spike features determining ‘host jump’ of coronaviruses SARS-CoV, MERS-CoV, and beyond. Trends Microbiol 23 (2015), 468–478.
47. [47] Dupinay, T., Gheit, T., Roques, P., Cova, L., Chevallier-Queyron, P., Tasahsu, S.I., et al. Discovery of naturally occurring transmissible chronic hepatitis B virus infection among Macaca fascicularis from Mauritius Island. Hepatology 58 (2013), 1610–1620.
48. [48] Yan, H., Peng, B., He, W., Zhong, G., Qi, Y., Ren, B., et al. Molecular determinants of hepatitis B and D virus entry restriction in mouse sodium taurocholate cotransporting polypeptide. J Virol 87 (2013), 7977–7991.
49. [49] He, W., Ren, B., Mao, F., Jing, Z., Li, Y., Liu, Y., Hepatitis D virus infection of mice expressing human sodium taurocholate co-transporting polypeptide. PLoS Pathog, 2015, 10.1371/journal.ppat.1004840.
50. [50] Lempp, F.A., Mutz, P., Lipps, C., Wirth, D., Bartenschlager, R., Urban, S., Evidence that hepatitis B virus replication in mouse cells is limited by the lack of a host cell dependency factor. J Hepatol 64 (2016), 556–564.
51. [51](a) Cui, X., Guo, J.T., Hu, J., Hepatitis B virus covalently closed circular DNA formation in immortalized mouse hepatocytes associated with nucleocapsid destabilization. J Virol 89 (2015), 9021–9028.
52. [51](b) Lempp, F.A., Qu, B., Wang, Y.X., Urban, S., Hepatitis, B., Virus infection of a mouse hepatic cell line reconstituted with human sodium taurocholate cotransporting polypeptide. J Virol, 2016, 10.1128/JVI.
53. [52] Verrier, E.R., Colpitts, C.C., Bach, C., Heydmann, L., Weiss, A., Renaud, M., et al. A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses. Hepatology 63 (2016), 35–48.
54. [53] Urban, S., Bartenschlager, R., Kubitz, R., Zoulim, F., Strategies to inhibit entry of HBV and HDV into hepatocytes. Gastroenterology 147 (2014), 48–64.
55. [54] Yan, H., Liu, Y., Sui, J., Li, W., NTCP opens the door for hepatitis B virus infection. Antiviral Res 121 (2015), 24–30.
56. [55] Zeisel, M.B., Lucifora, J., Mason, W.S., Sureau, C., Beck, J., Levrero, M., et al. Towards an HBV cure: state-of-the-art and unresolved questions-report of the ANRS workshop on HBV cure. Gut 64 (2015), 1314–1326.
57. [56] Guo, J.T., Guo, H., Metabolism and function of hepatitis B virus cccDNA: Implications for the development of cccDNA-targeting antiviral therapeutics. Antiviral Res 122 (2015), 91–100.
58. [57] Tropberger, P., Mercier, A., Robinson, M., Zhong, W., Ganem, D.E., Holdorf, M., Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual chromatin organization amenable to epigenetic manipulation. Proc Natl Acad Sci U S A 112 (2015), E5715–E5724.
59. [58] Teissier, E., Penin, F., Pecheur, E.I., Targeting cell entry of enveloped viruses as an antiviral strategy. Molecules 16 (2011), 221–250.
60. [59] Iwami, S., Takeuchi, J.S., Nakaoka, S., Mammano, F., Clavel, F., Inaba, H., et al. Cell-to-cell infection by HIV contributes over half of virus infection. Elife, 4, 2015, 10.7554/eLife.08150.
61. [60] Henrich, T.J., Kuritzkes, D.R., HIV-1 entry inhibitors: recent development and clinical use. Curr Opin Virol 3 (2013), 51–57.
62. [61] von Recum, H.A., Pokorski, J.K., Peptide and protein-based inhibitors of HIV-1 co-receptors. Exp Biol Med (Maywood) 238 (2013), 442–449.
63. [62] Eggink, D., Berkhout, B., Sanders, R.W., Inhibition of HIV-1 by fusion inhibitors. Curr Pharm Des 16 (2010), 3716–3728.
64. [63] Lutgehetmann, M., Mancke, L.V., Volz, T., Helbig, M., Allweiss, L., Bornscheuer, T., et al. Humanized chimeric uPA mouse model for the study of hepatitis B and D virus interactions and preclinical drug evaluation. Hepatology 55 (2012), 685–694.
65. [64] Lutgehetmann, M., Volz, T., Kopke, A., Broja, T., Tigges, E., Lohse, A.W., et al. In vivo proliferation of hepadnavirus-infected hepatocytes induces loss of covalently closed circular DNA in mice. Hepatology 52 (2010), 16–24.
66. [65] Corti, D., Bianchi, S., Vanzetta, F., Minola, A., Perez, L., Agatic, G., et al. Cross-neutralization of four paramyxoviruses by a human monoclonal antibody. Nature 501 (2013), 439–443.
67. [66] Corti, D., Lanzavecchia, A., Broadly neutralizing antiviral antibodies. Annu Rev Immunol 31 (2013), 705–742.
68. [67] Marasco, W.A., Sui, J., The growth and potential of human antiviral monoclonal antibody therapeutics. Nat Biotechnol 25 (2007), 1421–1434.
69. [68] Katz, L.H., Paul, M., Guy, D.G., Tur-Kaspa, R., Prevention of recurrent hepatitis B virus infection after liver transplantation: hepatitis B immunoglobulin, antiviral drugs, or both? Systematic review and meta-analysis. Transpl Infect Dis 12 (2010), 292–308.
70. [69] Mailly, L., Xiao, F., Lupberger, J., Wilson, G.K., Aubert, P., Duong, F.H., et al. Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody. Nat Biotechnol 33 (2015), 549–554.
71. [70] Asabe, S., Wieland, S.F., Chattopadhyay, P.K., Roederer, M., Engle, R.E., Purcell, R.H., et al. The size of the viral inoculum contributes to the outcome of hepatitis B virus infection. J Virol 83 (2009), 9652–9662.
72. [71] Lamas Longarela, O., Schmidt, T.T., Schoneweis, K., Romeo, R., Wedemeyer, H., Urban, S., et al. Proteoglycans act as cellular hepatitis delta virus attachment receptors. PLoS One, 8, 2013, e58340.
73. [72] Leistner, C.M., Gruen-Bernhard, S., Glebe, D., Role of glycosaminoglycans for binding and infection of hepatitis B virus. Cell Microbiol 10 (2008), 122–133.
74. [73] Schulze, A., Gripon, P., Urban, S., Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans. Hepatology 46 (2007), 1759–1768.
75. [74] Nkongolo, S., Ni, Y., Lempp, F.A., Kaufman, C., Lindner, T., Esser-Nobis, K., et al. Cyclosporin A inhibits hepatitis B and hepatitis D virus entry by cyclophilin-independent interference with the NTCP receptor. J Hepatol 60 (2014), 723–731.
76. [75] Konig, A., Doring, B., Mohr, C., Geipel, A., Geyer, J., Glebe, D., Kinetics of the bile acid transporter and hepatitis B virus receptor Na+/taurocholate cotransporting polypeptide (NTCP) in hepatocytes. J Hepatol 61 (2014), 867–875.
77. [76] Veloso Alves Pereira, I., Buchmann, B., Sandmann, L., Sprinzl, K., Schlaphoff, V., Dohner, K., et al. Primary biliary acids inhibit hepatitis D virus (HDV) entry into human hepatoma cells expressing the sodium-taurocholate cotransporting polypeptide (NTCP). PLoS One, 10, 2015, e0117152.
78. [77] Doring, B., Lutteke, T., Geyer, J., Petzinger, E., The SLC10 carrier family: transport functions and molecular structure. Curr Top Membr 70 (2012), 105–168.
79. [78] Lucifora, J., Esser, K., Protzer, U., Ezetimibe blocks hepatitis B virus infection after virus uptake into hepatocytes. Antiviral Res 97 (2013), 195–197.
80. [79] Kim, R.B., Leake, B., Cvetkovic, M., Roden, M.M., Nadeau, J., Walubo, A., et al. Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity. J Pharmacol Exp Ther 291 (1999), 1204–1209.
81. [80] Watashi, K., Sluder, A., Daito, T., Matsunaga, S., Ryo, A., Nagamori, S., et al. Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP). Hepatology 59 (2014), 1726–1737.
82. [81] Treiber, A., Schneiter, R., Hausler, S., Stieger, B., Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos 35 (2007), 1400–1407.
83. [82] Bremer, C.M., Sominskaya, I., Skrastina, D., Pumpens, P., El Wahed, A.A., Beutling, U., et al. N-terminal myristoylation-dependent masking of neutralizing epitopes in the preS1 attachment site of hepatitis B virus. J Hepatol 55 (2011), 29–37.
84. [83] Sugita, T., Amano, K., Nakano, M., Masubuchi, N., Sugihara, M., Matsuura, T., Analysis of the serum bile Acid composition for differential diagnosis in patients with liver disease. Gastroenterol Res Pract, 2015, 2015, 717431.
85. [84] Kim, D.H., Ni, Y., Lee, S.H., Urban, S., Han, K.H., An anti-viral peptide derived from the preS1 surface protein of hepatitis B virus. BMB Rep 41 (2008), 640–644.
86. [85] Lempp, F.A., Urban, S., Inhibitors of hepatitis B virus attachment and entry. Intervirology 57 (2014), 151–157.
87. [86] Barrera, A., Guerra, B., Notvall, L., Lanford, R.E., Mapping of the hepatitis B virus pre-S1 domain involved in receptor recognition. J Virol 79 (2005), 9786–9798.
88. [87] Glebe, D., Attachment sites and neutralising epitopes of hepatitis B virus. Minerva Gastroenterol Dietol 52 (2006), 3–21.
89. [88] Bijsmans, I.T., Bouwmeester, R.A., Geyer, J., Faber, K.N., van de Graaf, S.F., Homo- and hetero-dimeric architecture of the human liver Na(+)-dependent taurocholate co-transporting protein. Biochem J 441 (2012), 1007–1015.