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Asialoglycoprotein receptor interacts with the preS1 domain of hepatitis B virus in vivo and in vitro

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Abstract

Background

The preS1 domain of the large envelope protein has been identified as an essential viral structure involved in hepatitis B virus (HBV) attachment. However, the cellular receptor(s) for HBV has not yet been identified.

Aims

To identify a cell-surface receptor for HBV, which could elucidate the molecular mechanism of HBV infection.

Methods

A novel yeast two-hybrid system was used to screen proteins interacting with the preS1 region of HBV. Their interaction was verified by yeast cotransformation, coimmunoprecipitation and mammalian two-hybrid assay, while their intracellular and tissue localization was analyzed by confocal microscopy and immunohistochemistry, respectively.

Results

Asialoglycoprotein receptor (ASGPR) interacted specifically and directly with the preS1 domain of HBV in vivo and in vitro. The levels of expression of preS1 and ASGPR in the liver were similar and correlated with each other.

Conclusions

ASGPR is a candidate receptor for HBV that mediates further steps of HBV entry.

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References

  1. Schulze A, Gripon P, Urban S (2007) Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans. Hepatology 46:1759–1768

    Article  PubMed  CAS  Google Scholar 

  2. Leistner CM, Gruen-Bernhard S, Glebe D (2008) Role of glycosaminoglycans for binding and infection of hepatitis B virus. Cell Microbiol 10:122–133

    PubMed  CAS  Google Scholar 

  3. Stibbe W, Gerlich WH (1983) Structural relationships between minor and major proteins of hepatitis B surface antigen. J Virol 46:626–629

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  5. Neurath AR, Seto B, Strick N (1989) Antibodies to synthetic peptides from the preS1 region of the hepatitis B virus (HBV) envelope (env) protein are virus-neutralizing and protective. Vaccine 7:234–236

    Article  PubMed  CAS  Google Scholar 

  6. Neurath AR, Kent SB, Strick N, Parker K (1986) Identification and chemical synthesis of a host cell receptor binding site on hepatitis B virus. Cell 46:429–436

    Article  PubMed  CAS  Google Scholar 

  7. Le Seyec J, Chouteau P, Cannie I, Guguen-Guillouzo C, Gripon P (1998) Role of the pre-S2 domain of the large envelope protein in hepatitis B virus assembly and infectivity. J Virol 72:5573–5578

    PubMed  CAS  Google Scholar 

  8. Paran N, Geiger B, Shaul Y (2001) HBV infection of cell culture: evidence for multivalent and cooperative attachment. EMBO J 20:4443–4453

    Article  PubMed  CAS  Google Scholar 

  9. Ishikawa T, Kuroki K, Lenhoff R, Summers J, Ganem D (1994) Analysis of the binding of a host cell surface glycoprotein to the preS protein of duck hepatitis B virus. Virology 202:1061–1064

    Article  PubMed  CAS  Google Scholar 

  10. Barrera A, Guerra B, Lee H, Lanford RE (2004) Analysis of host range phenotypes of primate hepadnaviruses by in vitro infections of hepatitis D virus pseudotypes. J Virol 78:5233–5243

    Article  PubMed  CAS  Google Scholar 

  11. Aronheim A (1997) Improved efficiency sos recruitment system: expression of the mammalian GAP reduces isolation of Ras GTPase false positives. Nucleic Acids Res 25:3373–3374

    Article  PubMed  CAS  Google Scholar 

  12. Aronheim A, Engelberg D, Li N, al-Alawi N, Schlessinger J, Karin M (1994) Membrane targeting of the nucleotide exchange factor Sos is sufficient for activating the Ras signaling pathway. Cell 78:949–961

    Article  PubMed  CAS  Google Scholar 

  13. Chang NS, Pratt N, Heath J, Schultz L, Sleve D, Carey GB, Zevotek N (2001) Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity. J Biol Chem 276:3361–3370

    Article  PubMed  CAS  Google Scholar 

  14. Chu CM, Liaw YF (1992) Intrahepatic expression of pre-S1 and pre-S2 antigens in chronic hepatitis B virus infection in relation to hepatitis B virus replication and hepatitis delta virus superinfection. Gut 33:1544–1548

    Article  PubMed  CAS  Google Scholar 

  15. Pontisso P, Ruvoletto MG, Tiribelli C, Gerlich WH, Ruol A, Alberti A (1992) The preS1 domain of hepatitis B virus and IgA cross-react in their binding to the hepatocyte surface. J Gen Virol 73:2041–2045

    Article  PubMed  CAS  Google Scholar 

  16. Petit MA, Capel F, Dubanchet S, Mabit H (1992) PreS1-specific binding proteins as potential receptors for hepatitis B virus in human hepatocytes. Virology 187:211–222

    Article  PubMed  CAS  Google Scholar 

  17. Neurath AR, Strick N, Sproul P (1992) Search for hepatitis B virus cell receptors reveals binding sites for interleukin 6 on the virus envelope protein. J Exp Med 175:461–469

    Article  PubMed  CAS  Google Scholar 

  18. Dash S, Rao KV, Panda SK (1992) Receptor for pre-S1(21–47) component of hepatitis B virus on the liver cell: role in virus cell interaction. J Med Virol 37:116–121

    Article  PubMed  CAS  Google Scholar 

  19. Budkowska A, Quan C, Groh F, Bedossa P, Dubreuil P, Bouvet JP, Pillot J (1993) Hepatitis B virus (HBV) binding factor in human serum: candidate for a soluble form of hepatocyte HBV receptor. J Virol 67:4316–4322

    PubMed  CAS  Google Scholar 

  20. Treichel U, Meyer zum Büschenfelde KH, Stockert RJ, Poralla T, Gerken G (1994) The asialoglycoprotein receptor mediates hepatic binding and uptake of natural hepatitis B virus particles derived from viraemic carriers. J Gen Virol 75:3021–3029

    Article  PubMed  CAS  Google Scholar 

  21. Treichel U, Meyer zum Büschenfelde KH, Dienes HP, Gerken G (1997) Receptor-mediated entry of hepatitis B virus particles into liver cells. Arch Virol 142:493–498

    Article  PubMed  CAS  Google Scholar 

  22. Owada T, Matsubayashi K, Sakata H, Ihara H, Sato S, Ikebuchi K, Kato T, Azuma H, Ikeda H (2006) Interaction between desialylated hepatitis B virus and asialoglycoprotein receptor on hepatocytes may be indispensable for viral binding and entry. J Viral Hepat 13:11–18

    Article  PubMed  CAS  Google Scholar 

  23. Ryu CJ, Cho DY, Gripon P, Kim HS, Guguen-Guillouzo C, Hong HJ (2000) An 80-kilodalton protein that binds to the pre-S1 domain of hepatitis B virus. J Virol 74:110–116

    Article  PubMed  CAS  Google Scholar 

  24. De Falco S, Ruvoletto MG, Verdoliva A, Ruvo M, Raucci A, Marino M, Senatore S, Cassani G, Alberti A, Pontisso P, Fassina G (2001) Cloning and expression of a novel hepatitis B virus-binding protein from HepG2 cells. J Biol Chem 276:36613–36623

    Article  PubMed  Google Scholar 

  25. Deng Q, Zhai JW, Michel ML, Zhang J, Qin J, Kong YY, Zhang XX, Budkowska A, Tiollais P, Wang Y, Xie YH (2007) Identification and characterization of peptides that interact with hepatitis B virus via the putative receptor binding site. J Virol 81:4244–4254

    Article  PubMed  CAS  Google Scholar 

  26. Li D, Wang XZ, Ding J, Yu JP (2005) NACA as a potential cellular target of hepatitis B virus preS1 protein. Dig Dis Sci 50:1156–1160

    Article  PubMed  CAS  Google Scholar 

  27. Lunbiao Cui, Yiyue Ge, Yuhua Qi, Shi Zhiyang, Jiao Yongjun, Xian Qi, Zhai Xiangjun, Wang Hua (2010) Identification of GRP75 as a novel PreS1 binding protein using a proteomics strategy. Braz J Microbiol 41:512–518

    Article  Google Scholar 

  28. Persing DH, Varmus HE, Ganem D (1987) The preS1 protein of hepatitis B virus is acylated at its amino terminus with myristic acid. J Virol 61:1672–1677

    PubMed  CAS  Google Scholar 

  29. Bruss V, Hagelstein J, Gerhardt E, Galle PR (1996) Myristylation of the large surface protein is required for hepatitis B virus in vitro infectivity. Virology 218:396–399

    Article  PubMed  CAS  Google Scholar 

  30. Gripon P, Le Seyec J, Rumin S, Guguen-Guillouzo C (1995) Myristylation of the hepatitis B virus large surface protein is essential for viral infectivity. Virology 213:292–299

    Article  PubMed  CAS  Google Scholar 

  31. De Falco S, Ruvo M, Verdoliva A, Scarallo A, Raimondo D, Raucci A, Fassina G (2001) N-terminal myristylation of HBV preS1 domain enhances receptor recognition. J Pept Res 57:390–400

    Article  PubMed  Google Scholar 

  32. Becker S, Spiess M, Klenk HD (1995) The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus. J Gen Virol 76:393–399

    Article  PubMed  CAS  Google Scholar 

  33. Junbo H, Li Q, Zaide W, Yunde H (1999) Receptor-mediated interleukin-2 gene transfer into human hepatoma cells. Int J Mol Med 3:601–608

    PubMed  CAS  Google Scholar 

  34. Neda H, Wu CH, Wu GY (1991) Chemical modification of an ecotropic murine leukemia virus results in redirection of its target cell specificity. J Biol Chem 266:14143–14146

    PubMed  CAS  Google Scholar 

  35. Kuroda S, Otaka S, Miyazaki T, Nakao M, Fujisawa Y (1992) Hepatitis B virus envelope L protein particles. Synthesis and assembly in Saccharomyces cerevisiae, purification and characterization. J Biol Chem 267:1953–1961

    PubMed  CAS  Google Scholar 

  36. Hadzic N, Alberti A, Portmann B, Vergani D (1991) Detection of hepatitis B virus pre-S1 and pre-S2 determinants in paraffin wax embedded liver tissue: Importance of reagents used. J Clin Pathol 44:554–557

    Article  PubMed  CAS  Google Scholar 

  37. Bock CT, Tillmann HL, Manns MP, Trautwein C (1999) The pre-S region determines the intracellular localization and appearance of hepatitis B virus. Hepatology 30:517–525

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Thanks go to our colleagues in the laboratories for providing advice and help. This study was funded by the National Natural Science Foundation of China (grant 30571649).

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Correspondence to Shu-mei Lin.

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Zhang, X., Lin, Sm., Chen, Ty. et al. Asialoglycoprotein receptor interacts with the preS1 domain of hepatitis B virus in vivo and in vitro . Arch Virol 156, 637–645 (2011). https://doi.org/10.1007/s00705-010-0903-x

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  • DOI: https://doi.org/10.1007/s00705-010-0903-x

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