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. 2011 Apr 7;26(2):131–138. doi: 10.1007/s12250-011-3190-0

Novel evidence suggests Hepatitis B virus surface proteins participate in regulation of HBV genome replication

Jian Qiu 1,2, Bo Qin 1,2, Simon Rayner 1, Chun-chen Wu 1, Rong-juan Pei 1, Song Xu 1, Yun Wang 1,✉, Xin-wen Chen 1
PMCID: PMC8222424  PMID: 21468936

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.

Key words: Hepatitis B virus (HBV), HBsAg, Truncated surface protein (TSPs), Site-directed mutagenesis, Alternative translation initiation

Footnotes

Foundation item: National Basic Research Program of China (2007CB512900).

These authors contributed equally to this work.

References

  • 1.Carman W. F. The clinical significance of surface antigen variants of hepatitis b virus. J Viral Hepat. 1997;4(Suppl1):11–20. doi: 10.1111/j.1365-2893.1997.tb00155.x. [DOI] [PubMed] [Google Scholar]
  • 2.Chua P. K., Wang R. Y., Lin M. H., et al. 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. 2005;79(21):13483–13496. doi: 10.1128/JVI.79.21.13483-13496.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Cooreman M. P., Leroux-Roels G., Paulij W. P. Vaccine- and hepatitis b immune globulin-induced escape mutations of hepatitis b virus surface antigen. J Biomed Sci. 2001;8(3):237–247. doi: 10.1007/BF02256597. [DOI] [PubMed] [Google Scholar]
  • 4.Gan R. B., Chu M. J., Shen L. P., et al. The complete nucleotide sequence of the cloned DNA of hepatitis b virus subtype adr in padr-1. Sci Sin B. 1987;30(5):507–521. [PubMed] [Google Scholar]
  • 5.Han J., Pan X., Gao Y., et al. Inhibition of hepatitis b virus replication by the internal fragment of hepatitis b core protein. Virus Res. 2010;150(1–2):129–134. doi: 10.1016/j.virusres.2010.03.005. [DOI] [PubMed] [Google Scholar]
  • 6.Heermann K. H., Goldmann U., Schwartz W., et al. Large surface proteins of hepatitis b virus containing the pre-s sequence. J Virol. 1984;52(2):396–402. doi: 10.1128/jvi.52.2.396-402.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Howard C. R., Allison L. M. Hepatitis b surface antigen variation and protective immunity. Intervirology. 1995;38(1–2):35–40. doi: 10.1159/000150412. [DOI] [PubMed] [Google Scholar]
  • 8.Khan N., Guarnieri M., Ahn S. H., et al. Modulation of hepatitis b virus secretion by naturally occurring mutations in the s gene. J Virol. 2004;78(7):3262–3270. doi: 10.1128/JVI.78.7.3262-3270.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Lei Y. C., Hao Y. H., Zhang Z. M., et al. Inhibition of hepatitis b virus replication by apobec3g in vitro and in vivo. World J Gastroenterol. 2006;12(28):4492–4497. doi: 10.3748/wjg.v12.i28.4492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Li Y., Chen J., Wu C., et al. Hepatitis b virus/hepatitis c virus upregulate angiopoietin-2 expression through mitogen-activated protein kinase pathway. Hepatol Res. 2010;40(10):1022–1033. doi: 10.1111/j.1872-034X.2010.00712.x. [DOI] [PubMed] [Google Scholar]
  • 11.Lin X., Yuan Z. H., Wu L., et al. A single amino acid in the reverse transcriptase domain of hepatitis b virus affects virus replication efficiency. J Virol. 2001;75(23):11827–11833. doi: 10.1128/JVI.75.23.11827-11833.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Locarnini S. Molecular virology of hepatitis b virus. Semin Liver Dis. 2004;24(Suppl1):3–10. doi: 10.1055/s-2004-828672. [DOI] [PubMed] [Google Scholar]
  • 13.Loffler-Mary H., Dumortier J., Klentsch-Zimmer C., et al. Hepatitis b virus assembly is sensitive to changes in the cytosolic s loop of the envelope proteins. Virology. 2000;270(2):358–367. doi: 10.1006/viro.2000.0268. [DOI] [PubMed] [Google Scholar]
  • 14.Nishikawa M., Ryo K., Kimura T., et al. Mutant of the pre-s and s region of HBV. Nippon Rinsho. 1995;53Suppl(Pt2):47–51. [PubMed] [Google Scholar]
  • 15.Peterson D. L., Roberts I. M., Vyas G. N. Partial amino acid sequence of two major component polypeptides of hepatitis b surface antigen. Proc Natl Acad Sci USA. 1977;74(4):1530–1534. doi: 10.1073/pnas.74.4.1530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Simon K., Lingappa V. R., Ganem D. Secreted hepatitis b surface antigen polypeptides are derived from a transmembrane precursor. J Cell Biol. 1988;107(6Pt1):2163–2168. doi: 10.1083/jcb.107.6.2163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Stibbe W., Gerlich W. H. Characterization of pre-s gene products in hepatitis b surface antigen. Dev Biol Stand. 1983;54:33–43. [PubMed] [Google Scholar]
  • 18.Stibbe W., Gerlich W. H. Structural relationships between minor and major proteins of hepatitis b surface antigen. J Virol. 1983;46(2):626–628. doi: 10.1128/jvi.46.2.626-628.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Torresi J. The virological and clinical significance of mutations in the overlapping envelope and polymerase genes of hepatitis b virus. J Clin Virol. 2002;25(2):97–106. doi: 10.1016/S1386-6532(02)00049-5. [DOI] [PubMed] [Google Scholar]
  • 20.Wu C., Zhang X., Tian Y., et al. 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. 2010;91(Pt2):483–492. doi: 10.1099/vir.0.012740-0. [DOI] [PubMed] [Google Scholar]
  • 21.Xu Z., Yen T. S., Wu L., et al. Enhancement of hepatitis b virus replication by its x protein in transgenic mice. J Virol. 2002;76(5):2579–2584. doi: 10.1128/jvi.76.5.2579-2584.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Yuan T. T., Sahu G. K., Whitehead W. E., et al. 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. 1999;73(7):5731–5740. doi: 10.1128/jvi.73.7.5731-5740.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Virologica Sinica are provided here courtesy of Wuhan Institute of Virology, Chinese Academy of Sciences

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