1887

Abstract

A self-modulating mechanism by the hepatitis C virus (HCV) core protein has been suggested to influence the level of HCV replication, but current data on this subject are contradictory. We examined the effect of wild-type and mutated core protein on HCV IRES- and cap-dependent translation. The wild-type core protein was shown to inhibit both IRES- and cap-dependent translation in an system. This effect was duplicated in a dose-dependent manner with a synthetic peptide representing amino acids 1–20 of the HCV core protein. This peptide was able to bind to the HCV IRES as shown by a mobility shift assay. In contrast, a peptide derived from the hepatitis B virus (HBV) core protein that contained a similar proportion of basic residues was unable to inhibit translation or bind the HCV IRES. A recombinant vaccinia–HCV core virus was used to examine the effect of the HCV core protein on HCV IRES-dependent translation in cells and this was compared with the effects of an HBV core-recombinant vaccinia virus. In CV-1 and HuH7 cells, the HCV core protein inhibited translation directed by the IRES elements of HCV, encephalomyocarditis virus and classical swine fever virus as well as cap-dependent translation, whereas in HepG2 cells, only HCV IRES-dependent translation was affected. Thus, the ability of the HCV core protein to selectively inhibit HCV IRES-dependent translation is cell-specific. N-terminal truncated (aa 1–20) HCV core protein that was expressed from a novel recombinant vaccinia virus in cells abrogated the inhibitory phenotype of the core protein , consistent with the above data.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.18697-0
2003-04-01
2020-07-08
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/4/vir840815.html?itemId=/content/journal/jgv/10.1099/vir.0.18697-0&mimeType=html&fmt=ahah

References

  1. Bantel H., Lugering A., Poremba C., Lugering N., Held J., Domscheke W., Schulze-Osthoff K.. 2001; Caspase activation correlates with the degree of inflammatory liver injury in chronic hepatitis C virus infection. Hepatology34:758–767
    [Google Scholar]
  2. Bartenschlager R., Lohmann V.. 2000; Replication of hepatitis C virus. J Gen Virol81:1631–1648
    [Google Scholar]
  3. Blight K. J., Kolykhalov A. A., Rice C. M.. 2000; Efficient initiation of HCV RNA replication in cell culture. Science290:1972–1974
    [Google Scholar]
  4. Boyle D. B., Coupar B. E., Both G. W.. 1985; Multiple-cloning-site plasmids for the rapid construction of recombinant poxviruses. Gene35:169–177
    [Google Scholar]
  5. Cohen B., Richmond J. E.. 1982; Electron microscopy of hepatitis B virus core antigen synthesized in E. coli . Nature296:677–678
    [Google Scholar]
  6. Furuya T., Lai M. M. C.. 1993; Three different cellular proteins bind to complementary sites on the 5′-end-positive and 3′-end-negative strands of mouse hepatitis virus RNA. J Virol67:7215–7222
    [Google Scholar]
  7. Gong Y., Trowbridge R., Macnaughton T. B., Westaway E. G., Shannon A. D., Gowans E. J.. 1996; Characterization of RNA synthesis during a one-step growth curve and of the replication mechanism of bovine viral diarrhoea virus. J Gen Virol77:2729–2736
    [Google Scholar]
  8. Gowans E. J.. 2000; Distribution of markers of hepatitis C virus infection throughout the body. Semin Liver Dis20:85–102
    [Google Scholar]
  9. Greive S. J.. 2001; Studies on the expression of the structural proteins of hepatitis C virus . PhD thesis University of Queensland; Australia:
  10. Greive S. J., Webb R. I., Mackenzie J. M., Gowans E. J.. 2002; Expression of the hepatitis C virus structural proteins in mammalian cells induces morphology similar to that in natural infection. J Viral Hepat9:9–17
    [Google Scholar]
  11. Honda M., Brown E. A., Lemon S. M.. 1996; Stability of a stem-loop involving the initiator AUG controls the efficiency of internal initiation of translation on hepatitis C virus RNA. RNA 2:955–968
    [Google Scholar]
  12. Ikeda M., Yi M., Li K., Lemon S. M.. 2002; Selectable subgenomic and genome-length dicistronic RNAs derived from an infectious molecular clone of the HCV-N strain of hepatitis C virus replicate efficiently in cultured Huh7 cells. J Virol76:2997–3006
    [Google Scholar]
  13. Kunkel M., Lorinczi M., Rijnbrand R., Lemon S. M., Watowich S. J.. 2001; Self-assembly of nucleocapsid-like particles from recombinant hepatitis C virus core protein. J Virol75:2119–2129
    [Google Scholar]
  14. Lai M. M. C., Ware C. F.. 1999; Hepatitis C virus core protein: possible roles in viral pathogenesis. Curr Top Microbiol Immunol242:117–134
    [Google Scholar]
  15. Laskus T., Radkowski M., Wang L. F., Vargas H., Rakela J.. 1998; Search for hepatitis C virus extrahepatic replication sites in patients with acquired immunodeficiency syndrome: specific detection of negative-strand viral RNA in various tissues. Hepatology28:1398–1401
    [Google Scholar]
  16. Lo S. Y., Selby M. J., Ou J. H.. 1996; Interaction between hepatitis C virus core protein and E1 envelope protein. J Virol70:5177–5182
    [Google Scholar]
  17. Lohmann V., Korner F., Koch J., Herian U., Theilmann L., Bartenschlager R.. 1999; Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science285:110–113
    [Google Scholar]
  18. Lott W. B., Takyar S. S., Tuppen J., Crawford D. H., Harrison M., Sloots T. P., Gowans E. J.. 2001; Vitamin B12 and hepatitis C: molecular biology and human pathology. Proc Natl Acad Sci U S A98:4916–4921
    [Google Scholar]
  19. McLauchlan J.. 2000; Properties of the hepatitis C virus core protein: a structural protein that modulates cellular processes. J Viral Hepat7:2–14
    [Google Scholar]
  20. Minton E. J., Smillie D., Neal K. R., Irving W. L., Underwood J. C., James V.. 1998; Association between MHC class II alleles and clearance of circulating hepatitis C virus. Members of the Trent Hepatitis C Virus Study Group. J Infect Dis178:39–44
    [Google Scholar]
  21. Muller H. M., Pfaff E., Goeser T., Kallinowski B., Solbach C., Theilmann L.. 1993; Peripheral blood leukocytes serve as a possible extrahepatic site for hepatitis C virus replication. J Gen Virol74:669–676
    [Google Scholar]
  22. Pietschmann T., Lohmann V., Kaul A., Krieger N., Rinck G., Rutter G., Strand D., Bartenschlager R.. 2002; Persistent and transient replication of full-length hepatitis C virus genomes in cell culture. J Virol76:4008–4021
    [Google Scholar]
  23. Ray R. B., Lagging L. M., Meyer K., Steele R., Ray R.. 1995; Transcriptional regulation of cellular and viral promoters by the hepatitis C virus core protein. Virus Res37:209–220
    [Google Scholar]
  24. Ray R. B., Steele R., Meyer K., Ray R.. 1997; Transcriptional repression of p53 promoter by hepatitis C virus core protein. J Biol Chem272:10983–10986
    [Google Scholar]
  25. Ray S. C., Wang Y. M., Laeyendecker O., Ticehurst J. R., Villano S. A., Thomas D. L.. 1999; Acute hepatitis C virus structural gene sequences as predictors of persistent viremia: hypervariable region 1 as a decoy. J Virol73:2938–2946
    [Google Scholar]
  26. Rijnbrand R. C., Lemon S. M.. 2000; Internal ribosome entry site-mediated translation in hepatitis C virus replication. Curr Top Microbiol Immunol242:85–116
    [Google Scholar]
  27. Robertson B., Myers G., Howard C.. 14 other authors 1998; Classification, nomenclature, and database development for hepatitis C virus (HCV) and related viruses: proposals for standardization. International Committee on Virus Taxonomy. Arch Virol143:2493–2503
    [Google Scholar]
  28. Santolini E., Migliaccio G., La Monica N.. 1994; Biosynthesis and biochemical properties of the hepatitis C virus core protein. J Virol68:3631–3641
    [Google Scholar]
  29. Shimoike T., Mimori S., Tani H., Matsuura Y., Miyamura T.. 1999; Interaction of hepatitis C virus core protein with viral sense RNA and suppression of its translation. J Virol73:9718–9725
    [Google Scholar]
  30. Shrivastava A., Manna S. K., Ray R., Aggarwal B. B.. 1998; Ectopic expression of hepatitis C virus core protein differentially regulates nuclear transcription factors. J Virol72:9722–9728
    [Google Scholar]
  31. Simmonds P.. 1995; Variability of hepatitis C virus. Hepatology21:570–583
    [Google Scholar]
  32. Trowbridge R., Gowans E. J.. 1998; Molecular cloning of an Australian isolate of hepatitis C virus. Arch Virol143:501–511
    [Google Scholar]
  33. Wang Y. H., Trowbridge R., Gowans E. J.. 1997; Expression and interaction of the hepatitis C virus structural proteins and the 5′ untranslated region in baculovirus infected cells. Arch Virol142:2211–2223
    [Google Scholar]
  34. Wang T. H., Rijnbrand R. C., Lemon S. M.. 2000; Core protein-coding sequence, but not core protein, modulates the efficiency of cap-independent translation directed by the internal ribosome entry site of hepatitis C virus. J Virol74:11347–11358
    [Google Scholar]
  35. World Health Organisation 1999; Global surveillance and control of hepatitis C. Report of a WHO Consultation organized in collaboration with the Viral Hepatitis Prevention Board, Antwerp. Belgium. J Viral Hepat6:35–47
    [Google Scholar]
  36. Zhang J., Yamada O., Yoshida H., Iwai T., Araki H.. 2002; Autogenous translation inhibition of core protein: implication for switch from translation to RNA replication in hepatitis C virus. Virology293:141–150
    [Google Scholar]
  37. Zibert A., Meisel H., Kraas W., Schulz A., Jung G., Roggendorf M.. 1997; Early antibody response against hypervariable region 1 is associated with acute self-limiting infections of hepatitis C virus. Hepatology25:1245–1249
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.18697-0
Loading
/content/journal/jgv/10.1099/vir.0.18697-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error