Citation: Jian Qiu, Bo Qin, Simon Rayner, Chun-chen Wu, Rong-juan Pei, Song Xu, Yun Wang, Xin-wen Chen. Novel Evidence Suggests Hepatitis B Virus Surface Proteins Participate in Regulation of HBV Genome Replication* .VIROLOGICA SINICA, 2011, 26(2) : 131-138.  http://dx.doi.org/10.1007/s12250-011-3190-0

Novel Evidence Suggests Hepatitis B Virus Surface Proteins Participate in Regulation of HBV Genome Replication*

cstr: 32224.14.s12250-011-3190-0
  • Corresponding author: Xin-wen Chen, wangyun@wh.iov.cn
  • Received Date: 14 February 2011
    Accepted Date: 02 March 2011
    Available online: 01 April 2011

    Fund Project: National Basic Research Program of China 2007CB512900

  • Naturally occurring mutations in surface proteins of Hepatitis B virus (HBV) usually result in altered hepatitis B surface antigen (HBsAg) secretion efficiency. In the present study, we reported two conserved residues, M75 and M103 with respect to HBsAg, mutations of which not only attenuated HBsAg secretion (M75 only), but also suppressed HBV genome replication without compromising the overlapping p-gene product. We also found M75 and M103 can initiate truncated surface protein (TSPs) synthesis upon over-expression of full-length surface proteins, which may possibly contribute to HBV genome replication. However, attempts to rescue replication- defective HBV mutant by co-expression of TSPs initiated from M75 or M103 were unsuccessful, which indicated surface proteins rather than the putative TSPs were involved in regulation of HBV genome replication.

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    1. Carman W F. 1997. The clinical significance of surface antigen variants of hepatitis b virus. J Viral Hepat, 4 Suppl 1: 11-20.

    2. Chua P K, Wang R Y, Lin M H, et al. 2005. Reduced secretion of virions and hepatitis b virus (hbv) surface antigen of a naturally occurring hbv variant correlates with the accumulation of the small s envelope protein in the endoplasmic reticulum and golgi apparatus. J Virol, 79 (21): 13483-13496.
        doi: 10.1128/JVI.79.21.13483-13496.2005

    3. Cooreman M P, Leroux-Roels G, Paulij W P. 2001. Vaccine-and hepatitis b immune globulin-induced escape mutations of hepatitis b virus surface antigen. J Biomed Sci, 8 (3): 237-247.
        doi: 10.1007/BF02256597

    4. Gan R B, Chu M J, Shen L P, et al. 1987. The complete nucleotide sequence of the cloned DNA of hepatitis b virus subtype adr in padr-1. Sci Sin B, 30 (5): 507-521.

    5. Han J, Pan X, Gao Y, et al. 2010. Inhibition of hepatitis b virus replication by the internal fragment of hepatitis b core protein. Virus Res, 150 (1-2): 129-134.
        doi: 10.1016/j.virusres.2010.03.005

    6. Heermann K H, Goldmann U, Schwartz W, et al. 1984. Large surface proteins of hepatitis b virus containing the pre-s sequence. J Virol, 52 (2): 396-402.

    7. Howard C R, Allison L M. 1995. Hepatitis b surface antigen variation and protective immunity. Intervirology, 38 (1-2): 35-40.
        doi: 10.1159/000150412

    8. Khan N, Guarnieri M, Ahn S H, et al. 2004. Modulation of hepatitis b virus secretion by naturally occurring mutations in the s gene. J Virol, 78 (7): 3262-3270.
        doi: 10.1128/JVI.78.7.3262-3270.2004

    9. Lei Y C, Hao Y H, Zhang Z M, et al. 2006. Inhibition of hepatitis b virus replication by apobec3g in vitro and in vivo. World J Gastroenterol, 12 (28): 4492-4497.
        doi: 10.3748/wjg.v12.i28.4492

    10. Li Y, Chen J, Wu C, et al. 2010. Hepatitis b virus/ hepatitis c virus upregulate angiopoietin-2 expression through mitogen-activated protein kinase pathway. Hepatol Res, 40 (10): 1022-1033.
        doi: 10.1111/hep.2010.40.issue-10

    11. Lin X, Yuan Z H, Wu L, et al. 2001. A single amino acid in the reverse transcriptase domain of hepatitis b virus affects virus replication efficiency. J Virol, 75 (23): 11827-11833.
        doi: 10.1128/JVI.75.23.11827-11833.2001

    12. Locarnini S. 2004. Molecular virology of hepatitis b virus. Semin Liver Dis, 24 Suppl 1: 3-10.

    13. Loffler-Mary H, Dumortier J, Klentsch-Zimmer C, et al. 2000. Hepatitis b virus assembly is sensitive to changes in the cytosolic s loop of the envelope proteins. Virology, 270 (2): 358-367.
        doi: 10.1006/viro.2000.0268

    14. Nishikawa M, Ryo K, Kimura T, et al. 1995. Mutant of the pre-s and s region of HBV. Nippon Rinsho, 53 Suppl (Pt 2): 47-51.

    15. Peterson D L, Roberts I M, Vyas G N. 1977. Partial amino acid sequence of two major component polypeptides of hepatitis b surface antigen. Proc Natl Acad Sci USA, 74 (4): 1530-1534.
        doi: 10.1073/pnas.74.4.1530

    16. Simon K, Lingappa V R, Ganem D. 1988. Secreted hepatitis b surface antigen polypeptides are derived from a transmembrane precursor. J Cell Biol, 107 (6 Pt 1): 2163-2168.

    17. Stibbe W, Gerlich W H. 1983. Characterization of pre-s gene products in hepatitis b surface antigen. Dev Biol Stand, 54: 33-43.

    18. Stibbe W, Gerlich W H. 1983. Structural relationships between minor and major proteins of hepatitis b surface antigen. J Virol, 46 (2): 626-628.

    19. Torresi J. 2002. The virological and clinical significance of mutations in the overlapping envelope and polymerase genes of hepatitis b virus. J Clin Virol, 25 (2): 97-106.
        doi: 10.1016/S1386-6532(02)00049-5

    20. Wu C, Zhang X, Tian Y, et al. 2010. Biological significance of amino acid substitutions in hepatitis b surface antigen (hbsag) for glycosylation, secretion, antigenicity and immunogenicity of hbsag and hepatitis b virus replication. J Gen Virol, 91 (Pt 2): 483-492.

    21. Xu Z, Yen T S, Wu L, et al. 2002. Enhancement of hepatitis b virus replication by its x protein in transgenic mice. J Virol, 76 (5): 2579-2584.
        doi: 10.1128/jvi.76.5.2579-2584.2002

    22. Yuan T T, Sahu G K, Whitehead W E, et al. 1999. The mechanism of an immature secretion phenotype of a highly frequent naturally occurring missense mutation at codon 97 of human hepatitis b virus core antigen. J Virol, 73 (7): 5731-5740.

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    Novel Evidence Suggests Hepatitis B Virus Surface Proteins Participate in Regulation of HBV Genome Replication*

      Corresponding author: Xin-wen Chen, wangyun@wh.iov.cn
    • 1. State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
    • 2. Graduate University of the Chinese Academy of Sciences, Beijing 100039, China
    Fund Project:  National Basic Research Program of China 2007CB512900

    Abstract: Naturally occurring mutations in surface proteins of Hepatitis B virus (HBV) usually result in altered hepatitis B surface antigen (HBsAg) secretion efficiency. In the present study, we reported two conserved residues, M75 and M103 with respect to HBsAg, mutations of which not only attenuated HBsAg secretion (M75 only), but also suppressed HBV genome replication without compromising the overlapping p-gene product. We also found M75 and M103 can initiate truncated surface protein (TSPs) synthesis upon over-expression of full-length surface proteins, which may possibly contribute to HBV genome replication. However, attempts to rescue replication- defective HBV mutant by co-expression of TSPs initiated from M75 or M103 were unsuccessful, which indicated surface proteins rather than the putative TSPs were involved in regulation of HBV genome replication.