Skip to main content
Log in

Molecular characterization of suppression of hepatitis B virus transcription by hepatitis C virus core protein

  • Published:
Science in China Series C: Life Sciences Aims and scope Submit manuscript

Abstract

To further elucidate the molecular mechanisms underlying the suppression of hepatitis B virus (HBV) expression by the hepatitis C virus (HCV) core protein, five molecular clones of HCV cDNA sequence containing the 5′ noncoding (5′NC) and the core regions have been isolated from Chinese HBV- and HCV-coinfected patients. Sequence comparison and phylogenetic analysis showed that the HCV sequence cloned from coinfected individuals is indistinguishable from that identified in other patients. Cotransfection assay confirmed that the core protein expressed from one of the cloned sequence is capable of suppressing the expression of hepatitis B surface and e antigens (HBsAg and HBeAg, respectively). Deletion mapping revealed that the Cterminal hydrophobic region of the HCV. core is necessary for the suppression. Results from reporter assays demonstrated that HCV core protein interacts with the HBV C promoter and enhancer II elements and down-regulates the transcription of HBV as well as other cellular and heterologous viral genes in both hepatic and non-hepatic cell lines. Taken together, the findings suggest HCV core protein as a multifunctional negative regulator of transcription critically involved in the molecular interactions between HBV and HCV, and between HCV and the cell.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hou, Y.-D., Jin, D.-Y.,Current Tropics in Molecular Virology(in Chinese), Beijing: Science Press, 1994, 214–266.

    Google Scholar 

  2. Shih, C. -M., Lo, S. J., Miyarnura, T.et al., Suppression of hepatitis B virus expression and replication by hepatitis C virus core protein in HUH-7 cells,J. Virol., 1991, 67(10)3823.

    Google Scholar 

  3. Shih, C.-M., Chen, C.M., Chen, S.-Y.et al., Modulation of the trans-suppression activky of hepatitis C virus core protein by phosphorylation,J. Virol., 1995, 69(2): 1160.

    PubMed  CAS  Google Scholar 

  4. Santolini, E., Migliaccio, G., La Monica, N., Biosynthesis and biochemical properties of the hepatitis C virus core protein,J. Virol., 1994, 68:3631.

    PubMed  CAS  Google Scholar 

  5. Ravaggi, A., Natoli, G., Primi, D.et al., Intranuclear localization of full length and truncated hepatitis C virus core protein expressed in mammaliam cells,J. Hepatol., 1994, 10:-833.

    Article  Google Scholar 

  6. Lo, S.Y., Masiarz, F., Hwang, S.B.et al., Differential subcellular localization of hepatitis C virus core gene products,Virology. 1995, 213:455.

    Article  PubMed  CAS  Google Scholar 

  7. Suzuki, R., Matsuura, Y., Suzuki, T.et al., Nuclear localization of the truncated hepatitis C virus core protein with its hydrophobic C terminus deleted,J. Gen. Virol., 1995, 76: 53.

    Article  PubMed  CAS  Google Scholar 

  8. Matsymoto, M., Hwang, S. B., Jeng, K.-S.et al., Homotypic interaction and multimerization of hepatitis C virus core protein,Virology, 1996, 218:43.

    Article  Google Scholar 

  9. Dusheiko, G. M., Simmonds, P., Sequence variability of hepatitis C virus and its clinical relevance,J. Vim1 Hepatitis, 1994, l(1):1.

    Google Scholar 

  10. Ohba, K., Mimkami, M., Ohno, T.et al., Classification of hepatitis C virus into major types and subtypes based on molecular evolutionary analysis,Virus Res., 1995, 36:201.

    Article  PubMed  CAS  Google Scholar 

  11. Galibert, P., Mandart, E., Fitoussi, F.et al., Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned inE.coli, Nature, 1979, 281:646.

    Article  PubMed  CAS  Google Scholar 

  12. Lechner, M.S., Laimins, L. A., Inhibition of p53 DNA binding by human papilloma virus E6 protein,J. Virol., 1994, 68(7):462.

    Google Scholar 

  13. Sodroshi, J.G., Rosen, C. A.. Haseltine, W. A., Trans-acting transcriptional activation of the long terminal repeat of human T-lymphotropic virus in infected cells,Science, 1984, 225:381.

    Article  Google Scholar 

  14. Gendelman, H.E., Phelps, W., Feigenbaum, L.et al., Trans-activation of the human immunodeficiency virus long terminal repeat by DNA viruses,Proc. Natl. Acad. Sci. USA, 1986, 83:9759.

    Article  PubMed  CAS  Google Scholar 

  15. Jin, L., Lei, M., Limitations of evolutionary parsimony method of phylogenetic analysis,Mol. Biol. Evol., 1990, 7(1): 82.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work is partly supported by grant 85-916-01-03 (1990–1994) to Jin Dong-Yan for the development of diagnostic reagents for the infection of hepatitis C virus, Eighth National Five-Year Plan for the Advancement of Medical Science and Technology, the State Commission of Science and Technology.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, H., Yan, Z., Hou, Y. et al. Molecular characterization of suppression of hepatitis B virus transcription by hepatitis C virus core protein. Sci. China Ser. C.-Life Sci. 40, 648–656 (1997). https://doi.org/10.1007/BF02882696

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02882696

Keywords

Navigation