Digestive Diseases

Clinical Relevance of Bile Acid Metabolism and Transport

Sodium Taurocholate Cotransporting Polypeptide Acts as a Receptor for Hepatitis B and D Virus

Yan H. ยท Li W.

Author affiliations

National Institute of Biological Sciences, Beijing, China

Keywords: Bile acidsHepatitis B virusHost rangeSodium taurocholate cotransporting polypeptideViral pathogenesis

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Dig Dis 2015;33:388-396
https://doi.org/10.1159/000371692

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Article / Publication Details

First-Page Preview
Abstract of Clinical Relevance of Bile Acid Metabolism and Transport

Published online: May 27, 2015
Issue release date: May 2015

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 0

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: https://www.karger.com/DDI

Abstract

Infection of hepatitis B virus (HBV) remains a major public health problem worldwide. Understanding the viral infection and developing antivirals against HBV have been hampered by the lack of convenient culture systems and animal models for the infection. Sodium taurocholate cotransporting polypeptide (NTCP), a key bile acid transporter expressed in liver, was recently identified as a critical receptor for viral entry of HBV and its satellite virus hepatitis D virus (HDV). This finding enabled a reliable cell culture system for the viruses. Detailed studies have shown that NTCP is the major determinant for the species specificity of HBV and HDV at entry level. NTCP is responsible for most sodium-dependent bile salt uptake in liver. The molecular determinant critical for HBV/HDV infection overlaps with that for bile acids transporting on NTCP. We evaluated bile acids as potential antivirals for HBV and HDV infection, and developed bile acid derivatives that effectively block taurocholate transporting as well as viral infections. The discovery that NTCP acts as a receptor for HBV has opens a new door for future studies towards the ultimate goal of curative treatment of HBV infection.

ยฉ 2015 S. Karger AG, Basel



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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;30:2212-2219.
    External Resources
  2. Beasley RP, Hwang LY, Lin CC, Chien CS: Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22,707 men in Taiwan. Lancet 1981;2:1129-1133.
    External Resources
  3. Hughes SA, Wedemeyer H, Harrison PM: Hepatitis delta virus. Lancet 2011;378:73-85.
    External Resources
  4. Seeger C, Mason WS: Hepatitis B virus biology. Microbiol Mol Biol Rev 2000;64:51-68.
    External Resources
  5. Delaney WE 4th: Molecular virology of chronic hepatitis B and C: parallels, contrasts and impact on drug development and treatment outcome. Antiviral Res 2013;99:34-48.
    External Resources
  6. European Association for the Study of the Liver: EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol 2012;57:167-185.
    External Resources
  7. Niederau C, Heintges T, Lange S, Goldmann G, Niederau CM, Mohr L, Haussinger D: Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J Med 1996;334:1422-1427.
    External Resources
  8. Wong DK, Cheung AM, O'Rourke K, Naylor CD, Detsky AS, Heathcote J: Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis. Ann Intern Med 1993;119:312-323.
    External Resources
  9. Wong VW, Chan HL: Chronic hepatitis B: a treatment update. Semin Liver Dis 2013;33:122-129.
    External Resources
  10. Schulze A, Gripon P, Urban S: Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans. Hepatology 2007;46:1759-1768.
    External Resources
  11. Leistner CM, Gruen-Bernhard S, Glebe D: Role of glycosaminoglycans for binding and infection of hepatitis B virus. Cell Microbiol 2008;10:122-133.
    External Resources
  12. Glebe D, Urban S: Viral and cellular determinants involved in hepadnaviral entry. World J Gastroenterol 2007;13:22-38.
    External Resources
  13. Gripon P, Rumin S, Urban S, Le Seyec J, Glaise D, Cannie I, Guyomard C, Lucas J, Trepo C, Guguen-Guillouzo C: Infection of a human hepatoma cell line by hepatitis B virus. Proc Natl Acad Sci USA 2002;99:15655-15660.
    External Resources
  14. 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;213:292-299.
    External Resources
  15. 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;73:2052-2057.
    External Resources
  16. 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;75:11565-11572.
    External Resources
  17. 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;81:5841-5849.
    External Resources
  18. 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;79:1613-1622.
    External Resources
  19. Glebe D, Urban S, Knoop EV, Cag N, Krass P, Grun S, Bulavaite A, Sasnauskas K, Gerlich WH: Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and Tupaia hepatocytes. Gastroenterology 2005;129:234-245.
    External Resources
  20. Barrera A, Guerra B, Notvall L, Lanford RE: Mapping of the hepatitis B virus pre-S1 domain involved in receptor recognition. J Virol 2005;79:9786-9798.
    External Resources
  21. Engelke M, Mills K, Seitz S, Simon P, Gripon P, Schnolzer M, Urban S: Characterization of a hepatitis B and hepatitis delta virus receptor binding site. Hepatology 2006;43:750-760.
    External Resources
  22. 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;84:1989-2000.
    External Resources
  23. Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H, Fu L, Song M, Chen P, Gao W, Ren B, Sun Y, Cai T, Feng X, Sui J, Li W: Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife 2012;1:e00049.
    External Resources
  24. Zhong G, Yan H, Wang H, He W, Jing Z, Qi Y, Fu L, Gao Z, Huang Y, Xu G, Feng X, Sui J, Li W: Sodium taurocholate cotransporting polypeptide mediates woolly monkey hepatitis B virus infection of Tupaia hepatocytes. J Virol 2013;87:7176-7184.
    External Resources
  25. Iwamoto M, Watashi K, Tsukuda S, Aly HH, Fukasawa M, Fujimoto A, Suzuki R, Aizaki H, Ito T, Koiwai O, Kusuhara H, Wakita T: Evaluation and identification of hepatitis B virus entry inhibitors using HepG2 cells overexpressing a membrane transporter NTCP. Biochem Biophys Res Commun 2014;443:808-813.
    External Resources
  26. Ni Y, Lempp FA, Mehrle S, Nkongolo S, Kaufman C, Falth M, Stindt J, Koniger C, Nassal M, Kubitz R, Sultmann H, Urban S: Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes. Gastroenterology 2014;146:1070-1083.
    External Resources
  27. 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 2014;61:867-875.
    External Resources
  28. Hagenbuch B, Dawson P: The sodium bile salt cotransport family SLC10. Pflugers Arch 2004;447:566-570.
    External Resources
  29. 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.
    External Resources
  30. Anwer MS: Cellular regulation of hepatic bile acid transport in health and cholestasis. Hepatology 2004;39:581-590.
    External Resources
  31. Hu NJ, Iwata S, Cameron AD, Drew D: Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT. Nature 2011;478:408-411.
    External Resources
  32. Zhou X, Levin EJ, Pan Y, McCoy JG, Sharma R, Kloss B, Bruni R, Quick M, Zhou M: Structural basis of the alternating-access mechanism in a bile acid transporter. Nature 2014;505:569-573.
    External Resources
  33. Su JJ: Experimental infection of human hepatitis B virus (HBV) in adult tree shrews (in Chinese). Zhonghua Bing Li Xue Za Zhi 1987;16:103-106, 122.
    External Resources
  34. Yan R, Su J, Chen Z, Liu Y, Gan Y, Zhou D: A preliminary study on experimental infection of human hepatitis B virus in adult tree shrews. J Guangxi Med Univ 1984;1:10-15.
  35. 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;77:9511-9521.
    External Resources
  36. Walter E, Keist R, Niederost B, Pult I, Blum HE: Hepatitis B virus infection of Tupaia hepatocytes in vitro and in vivo. Hepatology 1996;24:1-5.
    External Resources
  37. Schieck A, Schulze A, Gahler C, Mรผller T, Haberkorn U, Alexandrov A, Urban S, Mier W: Hepatitis B virus hepatotropism is mediated by specific receptor recognition in the liver and not restricted to susceptible hosts. Hepatology 2013;58:43-53.
    External Resources
  38. Meier A, Mehrle S, Weiss TS, Mier W, Urban S: Myristoylated preS1-domain of the hepatitis B virus L-protein mediates specific binding to differentiated hepatocytes. Hepatology 2013;58:31-42.
    External Resources
  39. Dupinay T, Gheit T, Roques P, Cova L, Chevallier-Queyron P, Tasahsu SI, Le Grand R, Simon F, Cordier G, Wakrim L, Benjelloun S, Trepo C, Chemin I: Discovery of naturally occurring transmissible chronic hepatitis B virus infection among Macaca fascicularis from Mauritius Island. Hepatology 2013;58:1610-1620.
    External Resources
  40. Yan H, Peng B, He W, Zhong G, Qi Y, Ren B, Gao Z, Jing Z, Song M, Xu G, Sui J, Li W: Molecular determinants of hepatitis B and D virus entry restriction in mouse sodium taurocholate cotransporting polypeptide. J Virol 2013;87:7977-7991.
    External Resources
  41. Cattori V, Eckhardt U, Hagenbuch B: Molecular cloning and functional characterization of two alternatively spliced NTCP isoforms from mouse liver1. Biochim Biophys Acta 1999;1445:154-159.
    External Resources
  42. Li H, Zhuang Q, Wang Y, Zhang T, Zhao J, Zhang Y, Zhang J, Lin Y, Yuan Q, Xia N, Han J: HBV life cycle is restricted in mouse hepatocytes expressing human NTCP. Cell Mol Immunol 2014;11:175-183.
    External Resources
  43. Raney AK, Eggers CM, Kline EF, Guidotti LG, Pontoglio M, Yaniv M, McLachlan A: Nuclear covalently closed circular viral genomic DNA in the liver of hepatocyte nuclear factor 1 alpha-null hepatitis B virus transgenic mice. J Virol 2001;75:2900-2911.
    External Resources
  44. Guidotti LG, Matzke B, Schaller H, Chisari FV: High-level hepatitis B virus replication in transgenic mice. J Virol 1995;69:6158-6169.
    External Resources
  45. Yan H, Peng B, Liu Y, Xu G, He W, Ren B, Jing Z, Sui J, Li W: Viral entry of hepatitis B and D viruses and bile salts transportation share common molecular determinants on sodium taurocholate cotransporting polypeptide. J Virol 2014;88:3273-3284.
    External Resources
  46. Watashi K, Sluder A, Daito T, Matsunaga S, Ryo A, Nagamori S, Iwamoto M, Nakajima S, Tsukuda S, Borroto-Esoda K, Sugiyama M, Tanaka Y, Kanai Y, Kusuhara H, Mizokami M, Wakita T: Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP). Hepatology 2014;59:1726-1737.
    External Resources
  47. Kim RB, Leake B, Cvetkovic M, Roden MM, Nadeau J, Walubo A, Wilkinson GR: Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity. J Pharmacol Exp Ther 1999;291:1204-1209.
    External Resources
  48. Schroeder A, Eckhardt U, Stieger B, Tynes R, Schteingart CD, Hofmann AF, Meier PJ, Hagenbuch B: Substrate specificity of the rat liver Na(+)-bile salt cotransporter in Xenopus laevis oocytes and in CHO cells. Am J Physiol 1998;274:G370-G375.
    External Resources
  49. Volz T, Allweiss L, Ben MM, Warlich M, Lohse AW, Pollok JM, Alexandrov A, Urban S, Petersen J, Lutgehetmann M, Dandri M: The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus. J Hepatol 2013;58:861-867.
    External Resources
  50. Lutgehetmann M, Mancke LV, Volz T, Helbig M, Allweiss L, Bornscheuer T, Pollok JM, Lohse AW, Petersen J, Urban S, Dandri M: Humanized chimeric uPA mouse model for the study of hepatitis B and D virus interactions and preclinical drug evaluation. Hepatology 2012;55:685-694.
    External Resources
  51. Petersen J, Dandri M, Mier W, Lutgehetmann M, Volz T, von Weizsacker F, Haberkorn U, Fischer L, Pollok JM, Erbes B, Seitz S, Urban S: Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein. Nat Biotechnol 2008;26:335-341.
    External Resources
  52. Laupacis A, Keown PA, Ulan RA, McKenzie N, Stiller CR: Cyclosporin A: a powerful immunosuppressant. Can Med Assoc J 1982;126:1041-1046.
    External Resources
  53. Azer SA, Stacey NH: Differential effects of cyclosporin A on the transport of bile acids by human hepatocytes. Biochem Pharmacol 1993;46:813-819.
    External Resources
  54. Nkongolo S, Ni Y, Lempp FA, Kaufman C, Lindner T, Esser-Nobis K, Lohmann V, Mier W, Mehrle S, Urban S: Cyclosporin A inhibits hepatitis B and hepatitis D virus entry by cyclophilin-independent interference with the NTCP receptor. J Hepatol 2014;60:723-731.
    External Resources
  55. Watashi K, Shimotohno K: Cyclophilin and viruses: cyclophilin as a cofactor for viral infection and possible anti-viral target. Drug Target Insights 2007;2:9-18.
    External Resources
  56. Blanchet M, Sureau C, Labonte P: Use of FDA approved therapeutics with hNTCP metabolic inhibitory properties to impair the HDV lifecycle. Antiviral Res 2014;106:111-115.
    External Resources
  57. Kramer W, Stengelin S, Baringhaus KH, Enhsen A, Heuer H, Becker W, Corsiero D, Girbig F, Noll R, Weyland C: Substrate specificity of the ileal and the hepatic Na(+)/bile acid cotransporters of the rabbit. I. Transport studies with membrane vesicles and cell lines expressing the cloned transporters. J Lipid Res 1999;40:1604-1617.
    External Resources
  58. Oehler N, Volz T, Bhadra OD, Kah J, Allweiss L, Giersch K, Bierwolf J, Riecken K, Pollok JM, Lohse AW, Fehse B, Petersen J, Urban S, Lutgehetmann M, Heeren J, Dandri M: Binding of hepatitis B virus to its cellular receptor alters the expression profile of genes of bile acid metabolism. Hepatology 2014;60:1483-1493.
    External Resources
  59. Summers J, Jilbert AR, Yang W, Aldrich CE, Saputelli J, Litwin S, Toll E, Mason WS: Hepatocyte turnover during resolution of a transient hepadnaviral infection. Proc Natl Acad Sci USA 2003;100:11652-11659.
    External Resources
  60. Caruntu FA, Molagic V: cccDNA persistence during natural evolution of chronic VHB infection. Rom J Gastroenterol 2005;14:373-377.
    External Resources
  61. Guidotti LG, Rochford R, Chung J, Shapiro M, Purcell R, Chisari FV: Viral clearance without destruction of infected cells during acute HBV infection. Science 1999;284:825-829.
    External Resources
  62. Lucifora J, Xia Y, Reisinger F, Zhang K, Stadler D, Cheng X, Sprinzl MF, Koppensteiner H, Makowska Z, Volz T, Remouchamps C, Chou WM, Thasler WE, Huser N, Durantel D, Liang TJ, Munk C, Heim MH, Browning JL, Dejardin E, Dandri M, Schindler M, Heikenwalder M, Protzer U: Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA. Science 2014;343:1221-1228.
    External Resources
  63. Vaz FM, Paulusma CC, Huidekoper H, de Ru M, Lim C, Koster J, Ho-Mok K, Bootsma AH, Groen AK, Schaap FG, Oude Elferink RP, Waterham HR, Wanders RJ: Sodium taurocholate cotransporting polypeptide (SLC10A1) deficiency: conjugated hypercholanemia without a clear clinical phenotype. Hepatology 2015;61:260-267.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Clinical Relevance of Bile Acid Metabolism and Transport

Published online: May 27, 2015
Issue release date: May 2015

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 0

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: https://www.karger.com/DDI

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